The atmosphere at Old Trafford will be electric with United looking to overturn a 2-1 deficit in the Carling Cup semi-final second leg.
But with Manchester guaranteed some games should England be awarded the 2018 World Cup, Greater Manchester Police assistant chief constable Ian Hopkins hopes the fans will be on their best behaviour.
He said: "As one of the host cities for the 2018 World Cup bid, the second leg truly is a great day for Manchester to shine.
"We would ask that fans play their part by behaving sensibly and do the city proud.
"Yes there is going to be banter between the fans, but it is when that banter turns into aggressive and violent behaviour that the city of Manchester will suffer.
"I would like to stress that although the rivalry has always been there between the fans, previous derby matches have passed off largely peacefully and without major incident.
"I would ask that fans adhere to this tradition on Wednesday, regardless of what happened in the first leg.
"We will not hesitate to make arrests of troublemakers. Greater Manchester Police is very experienced at policing football matches and this game will be no exception."