Although Greater Manchester Police praised the respective supporters for their good behaviour at the FA Cup third-round tie at the Etihad Stadium in January, which United won 3-2, there have been problems in the past.
Twenty-nine people were arrested after the Carling Cup semi-final first-leg tie between the two sides two years ago, and with the latest meeting almost certainly going to decide the destination of this season's Premier League title, tensions are bound to be heightened.
United have been allocated 2,620 tickets for the fixture and there will be a heavy police presence on duty to ensure the match passes off without incident.
Any supporter caught with alcohol within the alcohol exclusion zone, stretching from the city centre to the stadium, will have it confiscated and police have also warned anyone arriving at the stadium under the influence of excess alcohol will be refused entry.
Chief Superintendent John O'Hare said: "As so much rests on this game, emotions will be running high and our main aim is to ensure the game is a safe and enjoyable experience for all fans.
"Greater Manchester Police will have the appropriate number of officers and resources within the ground and the surrounding areas to both deal with any incidents and offer reassurance to the public.
"The rivalry between the clubs really adds something extra to this fixture and should be embraced, but we must also ensure that this is not used as an excuse by some individuals to become involved in disorder.
"We want to make it clear to the minority who may be thinking of causing any trouble that we will clamp down hard on them. We want people to take responsibility for themselves and drink responsibly.
"We want to ensure that the city of Manchester, both of its clubs and its fans are remembered for the right reasons. We should celebrate the fact that the Premier League is coming to Manchester."