| Wednesday 18th February 2009 | |||
| 1st Leg | |||
| AaB Aalborg | 3-0 | Deportivo La Coruna | |
| Aston Villa | 1-1 | CSKA Moscow | |
| Bordeaux | 0-0 | Galatasaray | |
| Dinamo Kiev | 1-1 | Valencia | |
| NEC Nijmegen | 0-3 | SV Hamburg | |
| Olympiakos | 1-3 | Saint-Etienne | |
| Paris Saint-Germain | 2-0 | VfL Wolfsburg | |
| Sampdoria | 0-1 | Metalist Kharkiv | |
| Sporting Braga | 3-0 | Standard Liege | |
| Werder Bremen | 1-1 | AC Milan | |
| Zenit St Petersburg | 2-1 | VfB Stuttgart | |
| Thursday 19th February 2009 | |||
| 1st Leg | |||
| FC Copenhagen | 2-2 | Manchester City | |
| Fiorentina | 0-1 | Ajax | |
| Lech Poznan | 2-2 | Udinese | |
| Marseille | 0-1 | FC Twente Enschede | |
| Shakhtar Donetsk | 2-0 | Tottenham Hotspur | |
| Thursday 26th February 2009 | |||
| 2nd Leg | |||
| AC Milan | 2-2 | Werder Bremen | (3-3) |
| (Werder Bremen won on away goals) | |||
| Ajax | 1-1 | Fiorentina | (2-1) |
| CSKA Moscow | 2-0 | Aston Villa | (3-1) |
| Deportivo La Coruna | 1-3 | AaB Aalborg | (1-6) |
| FC Twente Enschede | 0-1 | Marseille | aet (1-1) |
| (Marseille won on penalties) | |||
| Galatasaray | 4-3 | Bordeaux | (4-3) |
| Manchester City | 2-1 | FC Copenhagen | (4-3) |
| Metalist Kharkiv | 2-0 | Sampdoria | (3-0) |
| Saint-Etienne | 2-1 | Olympiakos | (5-2) |
| Standard Liege | 1-1 | Sporting Braga | (1-4) |
| SV Hamburg | 1-0 | NEC Nijmegen | (4-0) |
| Tottenham Hotspur | 1-1 | Shakhtar Donetsk | (1-3) |
| Udinese | 2-1 | Lech Poznan | (4-3) |
| Valencia | 2-2 | Dinamo Kiev | (3-3) |
| (Dinamo Kiev won on away goals) | |||
| VfB Stuttgart | 1-2 | Zenit St Petersburg | (2-4) |
| VfL Wolfsburg | 1-3 | Paris Saint-Germain | (1-5) |
