| Tuesday 15th September 1981 | |||
| 1st Leg | |||
| Jeunesse Esch | 1-1 | Velez Mostar | |
| Wednesday 16th September 1981 | |||
| 1st Leg | |||
| Ajax | 1-3 | Tottenham Hotspur | |
| Ballymena United | 0-2 | Roma | |
| Barcelona | 4-1 | Trakia Plovdiv | |
| Dinamo Tbilisi | 2-0 | Grazer AK | |
| Dukla Prague | 3-0 | Rangers | |
| Eintracht Frankfurt | 2-0 | PAOK Salonika | |
| Fram Reykjavik | 2-1 | Dundalk | |
| KooTeePee Kotka | 0-0 | Bastia | |
| Lausanne-Sports | 2-1 | Kalmar | |
| Paralimni | 1-0 | Vasas Budapest | |
| SKA Rostov-na-Donu | 3-0 | Ankaragucu | |
| Swansea City | 0-1 | Lokomotive Leipzig | |
| Valerenga | 2-2 | Legia Warsaw | |
| Vejle | 2-1 | FC Porto | |
| Wednesday 23rd September 1981 | |||
| 1st Leg | |||
| Floriana | 1-3 | Standard Liege | |
| Tuesday 29th September 1981 | |||
| 2nd Leg | |||
| Tottenham Hotspur | 3-0 | Ajax | (6-1) |
| Wednesday 30th September 1981 | |||
| 2nd Leg | |||
| Ankaragucu | 0-2 | SKA Rostov-na-Donu | (0-5) |
| Bastia | 5-0 | KooTeePee Kotka | (5-0) |
| Dundalk | 4-0 | Fram Reykjavik | (5-2) |
| FC Porto | 3-0 | Vejle | (4-2) |
| Grazer AK | 2-2 | Dinamo Tbilisi | (2-4) |
| Kalmar | 3-2 | Lausanne-Sports | (4-4) |
| (Lausanne-Sports won on away goals) | |||
| Legia Warsaw | 4-1 | Valerenga | (6-3) |
| Lokomotive Leipzig | 2-1 | Swansea City | (3-1) |
| PAOK Salonika | 2-0 | Eintracht Frankfurt | aet (2-2) |
| (Eintracht Frankfurt won on penalties) | |||
| Rangers | 2-1 | Dukla Prague | (2-4) |
| Roma | 4-0 | Ballymena United | (6-0) |
| Trakia Plovdiv | 1-0 | Barcelona | (2-4) |
| Vasas Budapest | 8-0 | Paralimni | (8-1) |
| Velez Mostar | 6-1 | Jeunesse Esch | (7-2) |
| Thursday 1st October 1981 | |||
| 2nd Leg | |||
| Standard Liege | 9-0 | Floriana | (12-1) |
