Manchester City and Manchester United both face difficult ties in the Europa League following their .
City will face Portuguese Liga joint leaders FC Porto in the Round of 32 while United meet Dutch side Ajax.
Stoke City's reward for progressing from the group stage of the Europa League is a tie against Spanish outfit Valencia, who are third in La Liga.
In the Round of 16, Manchester City would not meet neighbours United.
Porto, who won the trophy last year under the guidance of now Chelsea boss Andre Villas-Boas, host Manchester City in the first leg before a return fixture at Etihad Stadium, while Manchester United will play in the Amsterdam ArenA first.
The games were scheduled for 16 and 23 February, 2012, but were altered after the draw because both Manchester clubs were due to play at home in the second legs.
United have a superior Uefa ranking so City have moved their second-leg tie against Porto to Wednesday 22 February at 1700 GMT to avoid clashing with the match at Old Trafford the following day. The earlier kick-off time also ensures the tie does not clash with the Champions League matches that night.
If City knock out FC Porto they would meet either Legia Warsaw or Sporting Lisbon, while United would face Lokomotiv Moscow or Athletic Bilbao if they overcome Ajax.
Stoke would play the winners of the tie between Trabzonspor and PSV Eindhoven in the last 16 if they get past Valencia on 8 and 16 March.
Manchester City manager Robert Mancini told the club's website: "Porto is probably the toughest game we could have.
"Manchester City against Porto feels like a Champions League game. I have come up against them as a player before and also a manager, they are a very good team and a very strong club in Europe.
"They are used to playing in Europe, in a great stadium. Not too many years ago they won the Champions League and also won the Europa League last year so they are a strong team."
United manager Sir Alex Ferguson added on manutd.com that the ties against Ajax would be a first for him: "Ajax are a good team and I've never faced them in competitive European football, I'm looking forward to it."
Elsewhere in the draw one of the stand-out matches is Lazio against Atletico Madrid, while the three other drop-in sides from the Champions League - Viktoria Plzen, Trabzonspor and Olympiakos - have been matched with Schalke, PSV Eindhoven and Rubin Kazan respectively.
EUROPA LEAGUE ROUND OF 32 DRAW
FC Porto v Manchester City [2nd leg now 22 Feb]
Ajax v Manchester United
Lokomotiv Moscow v Athletic Bilbao
SV Salzburg v Metalist Kharkiv
Stoke City v Valencia
Rubin Kazan v Olympiakos
AZ Alkmaar v Anderlecht
Lazio v Atletico Madrid
Steaua Bucharest v FC Twente
Plzen v FC Schalke
Wisla Krakow v Standard Liege
SC Braga v Besiktas [1st leg now 14 Feb]
Udinese v PAOK
Trabzonspor v PSV
Hannover v Club Brugge
Legia Warsaw v Sporting
Ties scheduled for 14/16 and 22/23 February
EUROPA LEAGUE ROUND OF 16 DRAW
SV Salzburg/Metalist v Rubin K/Olympiakos
Legia W/Sporting v Porto/Manchester City
Steaua/Twente v Plzen/Schalke
Wisla K/Standard L v Hannover/Club Brugge
Stoke/Valencia v Trabzonspor/PSV
Az Alkmaar/Andrelecht v Udinese/PAOK
Lazio/Atletico M v SC Braga/Besiktas
Ajax/Manchester United v Lokomotiv M/Ahtletic B
Ties scheduled for 8 and 15 March