| | FIXTURE | VENUE | GMT | LOCAL | POOL |
| | Fri, 24 September 2021 |
| | Lions v Zebre | Stadio Sergio Lanfranchi | 16:35 | 18:35 | Round 1 |
| | Cardiff Blues v Connacht | Cardiff Arms Park | 18:35 | 20:35 | Round 1 |
| | Glasgow Warriors v Ulster | Kingspan Stadium | 18:35 | 20:35 | Round 1 |
| |
| | Sat, 25 September 2021 |
| | Benetton Treviso v Stormers | Stadio Comunale Di Monigo | 12:00 | 14:00 | Round 1 |
| | Edinburgh v Scarlets | Edinburgh Rugby Stadium | 16:15 | 18:15 | Round 1 |
| | Bulls v Leinster | Aviva Stadium | 16:15 | 18:15 | Round 1 |
| | Munster v Sharks | Thomond Park | 18:35 | 20:35 | Round 1 |
| |
| | Sun, 26 September 2021 |
| | Gwent Dragons v Ospreys | Rodney Parade | 13:00 | 15:00 | Round 1 |
| |
| | Fri, 1 October 2021 |
| | Bulls v Connacht | The Sportsground | 18:35 | 20:35 | Round 2 |
| | Lions v Scarlets | Parc y Scarlets | 18:35 | 20:35 | Round 2 |
| |
| | Sat, 2 October 2021 |
| | Benetton Treviso v Edinburgh | Stadio Comunale Di Monigo | 13:00 | 15:00 | Round 2 |
| | Glasgow Warriors v Sharks | Scotstoun Stadium | 14:00 | 16:00 | Round 2 |
| | Ulster v Zebre | Stadio Sergio Lanfranchi | 16:15 | 18:15 | Round 2 |
| | Munster v Stormers | Thomond Park | 18:35 | 20:35 | Round 2 |
| | Cardiff Blues v Ospreys | Liberty Stadium | 18:35 | 20:35 | Round 2 |
| |
| | Sun, 3 October 2021 |
| | Gwent Dragons v Leinster | Rodney Parade | 13:00 | 15:00 | Round 2 |
| |
| | Fri, 8 October 2021 |
| | Benetton Treviso v Ulster | Kingspan Stadium | 18:35 | 20:35 | Round 3 |
| | Ospreys v Sharks | Liberty Stadium | 18:35 | 20:35 | Round 3 |
| |
| | Sat, 9 October 2021 |
| | Leinster v Zebre | RDS Arena | 12:00 | 14:00 | Round 3 |
| | Glasgow Warriors v Lions | Scotstoun Stadium | 14:05 | 16:05 | Round 3 |
| | Connacht v Gwent Dragons | The Sportsground | 16:15 | 18:15 | Round 3 |
| | Edinburgh v Stormers | Edinburgh Rugby Stadium | 16:15 | 18:15 | Round 3 |
| | Bulls v Cardiff Blues | Cardiff Arms Park | 18:35 | 20:35 | Round 3 |
| |
| | Sun, 10 October 2021 |
| | Munster v Scarlets | Parc y Scarlets | 13:00 | 15:00 | Round 3 |
| |
| | Fri, 15 October 2021 |
| | Gwent Dragons v Stormers | Rodney Parade | 18:35 | 20:35 | Round 4 |
| | Lions v Ulster | Kingspan Stadium | 18:35 | 20:35 | Round 4 |
| |
| | Sat, 16 October 2021 |
| | Glasgow Warriors v Zebre | Stadio Sergio Lanfranchi | 12:00 | 14:00 | Round 4 |
| | Benetton Treviso v Ospreys | Stadio Comunale Di Monigo | 14:05 | 16:05 | Round 4 |
| | Bulls v Edinburgh | Edinburgh Rugby Stadium | 16:15 | 18:15 | Round 4 |
| | Leinster v Scarlets | RDS Arena | 16:15 | 18:15 | Round 4 |
| | Cardiff Blues v Sharks | Cardiff Arms Park | 18:35 | 20:35 | Round 4 |
| | Connacht v Munster | Thomond Park | 18:35 | 20:35 | Round 4 |
| |
| | Fri, 22 October 2021 |
| | Benetton Treviso v Scarlets | Parc y Scarlets | 18:35 | 20:35 | Round 5 |
| | Glasgow Warriors v Leinster | Scotstoun Stadium | 18:35 | 20:35 | Round 5 |
| |
| | Sat, 23 October 2021 |
| | Edinburgh v Zebre | Stadio Sergio Lanfranchi | 12:00 | 14:00 | Round 5 |
| | Connacht v Ulster | The Sportsground | 16:15 | 18:15 | Round 5 |
| | Cardiff Blues v Gwent Dragons | Cardiff Arms Park | 16:15 | 18:15 | Round 5 |
| | Munster v Ospreys | Liberty Stadium | 18:35 | 20:35 | Round 5 |
| |
| | Fri, 26 November 2021 |
| | Connacht v Ospreys | The Sportsground | 19:35 | 21:35 | Round 6 |
| |
| | Sat, 27 November 2021 |
| | Benetton Treviso v Glasgow Warriors | Stadio Comunale Di Monigo | 13:00 | 15:00 | Round 6 |
| | Stormers v Zebre | DHL Stadium | 13:00 | 15:00 | Round 6 |
| | Scarlets v Sharks | Kings Park Stadium | 15:30 | 17:30 | Round 6 |
| | Edinburgh v Gwent Dragons | Rodney Parade | 17:15 | 19:15 | Round 6 |
| | Bulls v Munster | Loftus Versfeld | 17:45 | 19:45 | Round 6 |
| | Leinster v Ulster | RDS Arena | 20:00 | 22:00 | Round 6 |
| |
| | Sun, 28 November 2021 |
| | Cardiff Blues v Lions | Emirates Airline Park | 14:00 | 16:00 | Round 6 |
| |
| | Fri, 3 December 2021 |
| | Bulls v Scarlets | Loftus Versfeld | 17:35 | 19:35 | Round 7 |
| | Benetton Treviso v Edinburgh | Edinburgh Rugby Stadium | 19:35 | 21:35 | Round 7 |
| | Connacht v Leinster | RDS Arena | 19:45 | 21:45 | Round 7 |
| |
| | Sat, 4 December 2021 |
| | Sharks v Zebre | Kings Park Stadium | 13:00 | 15:00 | Round 7 |
| | Ospreys v Ulster | Liberty Stadium | 15:00 | 17:00 | Round 7 |
| | Lions v Munster | Emirates Airline Park | 15:30 | 17:30 | Round 7 |
| | Glasgow Warriors v Gwent Dragons | Scotstoun Stadium | 17:15 | 19:15 | Round 7 |
| | Cardiff Blues v Stormers | DHL Stadium | 17:45 | 19:45 | Round 7 |
| |
| | Fri, 24 December 2021 |
| | Benetton Treviso v Zebre | Stadio Sergio Lanfranchi | 13:00 | 15:00 | Round 8 |
| |
| | Sun, 26 December 2021 |
| | Cardiff Blues v Scarlets | Cardiff Arms Park | 15:00 | 17:00 | Round 8 |
| | Gwent Dragons v Ospreys | Liberty Stadium | 17:15 | 19:15 | Round 8 |
| | Connacht v Ulster | Kingspan Stadium | 17:15 | 19:15 | Round 8 |
| | Leinster v Munster | Thomond Park | 19:35 | 21:35 | Round 8 |
| |
| | Mon, 27 December 2021 |
| | Edinburgh v Glasgow Warriors | Scotstoun Stadium | 19:00 | 21:00 | Round 8 |
| |
| | Sat, 1 January 2022 |
| | Cardiff Blues v Gwent Dragons | Rodney Parade | 15:00 | 17:00 | Round 9 |
| | Connacht v Munster | The Sportsground | 17:15 | 19:15 | Round 9 |
| | Ospreys v Scarlets | Parc y Scarlets | 17:15 | 19:15 | Round 9 |
| | Leinster v Ulster | Kingspan Stadium | 19:35 | 21:35 | Round 9 |
| |
| | Sun, 2 January 2022 |
| | Benetton Treviso v Zebre | Stadio Comunale Di Monigo | 13:00 | 15:00 | Round 9 |
| | Edinburgh v Glasgow Warriors | Edinburgh Rugby Stadium | 14:00 | 16:00 | Round 9 |
| |
| | Fri, 7 January 2022 |
| | Leinster v Lions | RDS Arena | 19:35 | 21:35 | Round 10 |
| |
| | Sat, 8 January 2022 |
| | Benetton Treviso v Sharks | Stadio Comunale Di Monigo | 13:00 | 15:00 | Round 10 |
| | Cardiff Blues v Edinburgh | Edinburgh Rugby Stadium | 15:00 | 17:00 | Round 10 |
| | Bulls v Zebre | Stadio Sergio Lanfranchi | 15:00 | 17:00 | Round 10 |
| | Connacht v Stormers | The Sportsground | 17:00 | 19:00 | Round 10 |
| | Glasgow Warriors v Ospreys | Scotstoun Stadium | 17:15 | 19:15 | Round 10 |
| | Munster v Ulster | Thomond Park | 19:35 | 21:35 | Round 10 |
| | Gwent Dragons v Scarlets | Parc y Scarlets | 19:35 | 21:35 | Round 10 |
| |
| | Sat, 29 January 2022 |
| | Connacht v Glasgow Warriors | The Sportsground | 0:00 | 2:00 | Round 11 |
| | Benetton Treviso v Gwent Dragons | Rodney Parade | 0:00 | 2:00 | Round 11 |
| | Edinburgh v Ospreys | Liberty Stadium | 0:00 | 2:00 | Round 11 |
| | Scarlets v Ulster | Kingspan Stadium | 0:00 | 2:00 | Round 11 |
| | Munster v Zebre | Stadio Sergio Lanfranchi | 0:00 | 2:00 | Round 11 |
| | Bulls v Lions | Loftus Versfeld | 0:00 | 2:00 | Round 11 |
| | Sharks v Stormers | DHL Stadium | 0:00 | 2:00 | Round 11 |
| | Cardiff Blues v Leinster | Cardiff Arms Park | 0:00 | 2:00 | Round 11 |
| |
| | Sat, 5 February 2022 |
| | Lions v Sharks | Emirates Airline Park | 23:00 | 1:00 | Round 5 |
| | Bulls v Stormers | DHL Stadium | 23:00 | 1:00 | Round 5 |
| |
| | Sat, 12 February 2022 |
| | Bulls v Sharks | Loftus Versfeld | 0:00 | 2:00 | Round 8 |
| | Lions v Sharks | DHL Stadium | 0:00 | 2:00 | Round 8 |
| |
| | Sat, 19 February 2022 |
| | Bulls v Sharks | Kings Park Stadium | 0:00 | 2:00 | Round 12 |
| | Lions v Stormers | Emirates Airline Park | 0:00 | 2:00 | Round 12 |
| | Edinburgh v Munster | Thomond Park | 0:00 | 2:00 | Round 12 |
| | Connacht v Scarlets | Parc y Scarlets | 0:00 | 2:00 | Round 12 |
| | Gwent Dragons v Ulster | Rodney Parade | 0:00 | 2:00 | Round 12 |
| | Benetton Treviso v Glasgow Warriors | Scotstoun Stadium | 0:00 | 2:00 | Round 12 |
| | Cardiff Blues v Zebre | Cardiff Arms Park | 0:00 | 2:00 | Round 12 |
| | Leinster v Ospreys | RDS Arena | 0:00 | 2:00 | Round 12 |
| |
| | Sat, 5 March 2022 |
| | Lions v Sharks | Kings Park Stadium | 0:00 | 2:00 | Round 13 |
| | Bulls v Stormers | Loftus Versfeld | 0:00 | 2:00 | Round 13 |
| | Glasgow Warriors v Scarlets | Parc y Scarlets | 0:00 | 2:00 | Round 13 |
| | Cardiff Blues v Ulster | Kingspan Stadium | 0:00 | 2:00 | Round 13 |
| | Gwent Dragons v Munster | Thomond Park | 0:00 | 2:00 | Round 13 |
| | Connacht v Edinburgh | Edinburgh Rugby Stadium | 0:00 | 2:00 | Round 13 |
| | Benetton Treviso v Leinster | Stadio Comunale Di Monigo | 0:00 | 2:00 | Round 13 |
| | Ospreys v Zebre | Liberty Stadium | 0:00 | 2:00 | Round 13 |
| |
| | Sat, 19 March 2022 |
| | Bulls v Lions | Emirates Airline Park | 0:00 | 2:00 | Round 9 |
| | Sharks v Stormers | Kings Park Stadium | 0:00 | 2:00 | Round 9 |
| |
| | Sat, 26 March 2022 |
| | Stormers v Ulster | DHL Stadium | 0:00 | 2:00 | Round 14 |
| | Edinburgh v Sharks | Kings Park Stadium | 0:00 | 2:00 | Round 14 |
| | Bulls v Gwent Dragons | Loftus Versfeld | 0:00 | 2:00 | Round 14 |
| | Lions v Ospreys | Emirates Airline Park | 0:00 | 2:00 | Round 14 |
| | Benetton Treviso v Munster | Thomond Park | 0:00 | 2:00 | Round 14 |
| | Connacht v Leinster | The Sportsground | 0:00 | 2:00 | Round 14 |
| | Cardiff Blues v Glasgow Warriors | Cardiff Arms Park | 0:00 | 2:00 | Round 14 |
| | Scarlets v Zebre | Stadio Sergio Lanfranchi | 0:00 | 2:00 | Round 14 |
| |
| | Sat, 2 April 2022 |
| | Benetton Treviso v Connacht | Stadio Comunale Di Monigo | 23:00 | 1:00 | Round 15 |
| | Glasgow Warriors v Zebre | Scotstoun Stadium | 23:00 | 1:00 | Round 15 |
| | Leinster v Munster | RDS Arena | 23:00 | 1:00 | Round 15 |
| | Cardiff Blues v Scarlets | Parc y Scarlets | 23:00 | 1:00 | Round 15 |
| | Bulls v Ulster | Loftus Versfeld | 23:00 | 1:00 | Round 15 |
| | Edinburgh v Lions | Emirates Airline Park | 23:00 | 1:00 | Round 15 |
| | Gwent Dragons v Sharks | Kings Park Stadium | 23:00 | 1:00 | Round 15 |
| | Ospreys v Stormers | DHL Stadium | 23:00 | 1:00 | Round 15 |
| |
| | Sat, 23 April 2022 |
| | Glasgow Warriors v Stormers | DHL Stadium | 23:00 | 1:00 | Round 16 |
| | Connacht v Lions | Emirates Airline Park | 23:00 | 1:00 | Round 16 |
| | Benetton Treviso v Bulls | Loftus Versfeld | 23:00 | 1:00 | Round 16 |
| | Leinster v Sharks | Kings Park Stadium | 23:00 | 1:00 | Round 16 |
| | Gwent Dragons v Scarlets | Rodney Parade | 23:00 | 1:00 | Round 16 |
| | Edinburgh v Zebre | Edinburgh Rugby Stadium | 23:00 | 1:00 | Round 16 |
| | Cardiff Blues v Ospreys | Cardiff Arms Park | 23:00 | 1:00 | Round 16 |
| | Munster v Ulster | Kingspan Stadium | 23:00 | 1:00 | Round 16 |
| |
| | Sat, 30 April 2022 |
| | Leinster v Stormers | DHL Stadium | 23:00 | 1:00 | Round 17 |
| | Benetton Treviso v Lions | Emirates Airline Park | 23:00 | 1:00 | Round 17 |
| | Bulls v Glasgow Warriors | Loftus Versfeld | 23:00 | 1:00 | Round 17 |
| | Connacht v Sharks | Kings Park Stadium | 23:00 | 1:00 | Round 17 |
| | Ospreys v Scarlets | Liberty Stadium | 23:00 | 1:00 | Round 17 |
| | Cardiff Blues v Munster | Thomond Park | 23:00 | 1:00 | Round 17 |
| | Edinburgh v Ulster | Edinburgh Rugby Stadium | 23:00 | 1:00 | Round 17 |
| | Gwent Dragons v Zebre | Stadio Sergio Lanfranchi | 23:00 | 1:00 | Round 17 |
| |
| | Sat, 21 May 2022 |
| | Benetton Treviso v Cardiff Blues | Stadio Comunale Di Monigo | 23:00 | 1:00 | Round 18 |
| | Connacht v Zebre | The Sportsground | 23:00 | 1:00 | Round 18 |
| | Glasgow Warriors v Munster | Scotstoun Stadium | 23:00 | 1:00 | Round 18 |
| | Gwent Dragons v Lions | Rodney Parade | 23:00 | 1:00 | Round 18 |
| | Edinburgh v Leinster | RDS Arena | 23:00 | 1:00 | Round 18 |
| | Bulls v Ospreys | Liberty Stadium | 23:00 | 1:00 | Round 18 |
| | Scarlets v Stormers | Parc y Scarlets | 23:00 | 1:00 | Round 18 |
| | Sharks v Ulster | Kingspan Stadium | 23:00 | 1:00 | Round 18 |
