After a six-month break, hostilities between Liverpool and United resume on Sunday.
With United desperately looking for a morale-boosting win against a big team, and Liverpool hoping to confirm their status as serious title contenders, a lot is riding on the fixture for both teams.
For Vidic it is the last time he will be able to lead United out against the oldest rivals of the team which he has served so well for almost eight years.
The Serb has enjoyed mixed fortunes against Liverpool throughout his time at United. The imposing captain scored the winning goal against Brendan Rodgers' team last January, but he has also been sent off three times against the Reds.
Now that his departure to Inter Milan has been confirmed, he knows this will be his last chance to play in what he admits is one of the biggest matches in world football and he does not want to miss out.
"It's the sort of match you want to be involved in," the defender told United Uncovered.
"United against Liverpool is not just an English derby, it's worldwide.
"It's not just rivalry between two big clubs, it's between two cities. You feel that on the pitch - the tradition of the two clubs.
"Winning is a great feeling and losing is the worst feeling. But it's being watched all over the world and you want to be part of the show and part of the history."
Vidic and Rio Ferdinand rolled back the years to shut out Arsenal last month and they also helped United keep a clean sheet at Crystal Palace the following week.
But following the announcement that Vidic is off to Inter at the end of the season, manager David Moyes opted to use Chris Smalling and Phil Jones at centre-half against West Brom.
The duo played well in the 3-0 win and although Liverpool will present a far tougher challenge, Moyes has been happy with how Jones and Smalling took to the task of filling in for Vidic and Ferdinand at the Hawthorns.
"I'm pleased with the young boys," the United manager said.
"We've had great service from Rio and Vida and we're using them because we need their experience.
"With the amount of games we have coming up we're going to need them to be fit and healthy."
Although victory on Sunday would only reduce the gap between the two teams to eight points, the boost in morale would be huge.
To achieve that the United defence will have to neuter arguably the most dangerous attack in the Barclays Premier League.
Luis Suarez and Daniel Sturridge have scored 45 goals between them this season. Supported by such talented individuals as Philippe Coutinho, Raheem Sterling, Steven Gerrard and the rejuvenated Jordan Henderson, Liverpool are a formidable force.
But Marouane Fellaini, who knows all about big games against Liverpool after his time at Everton, thinks United also have a formidable front line.
"We have a lot of quality in attack - we have (Juan) Mata, (Wayne) Rooney, Adnan (Januzaj) and Robin (van Persie), and they offer a threat going forward" said Fellaini, who won just one of the 10 Merseyside derbies he played in.
"They give a lot of solutions in attacking positions so that's great for the team that they have that understanding. We scored three goals against West Brom and played well, so we're happy with that."
Fellaini was happy that United put their 2-0 defeat to Olympiacos behind them by beating the Baggies last week.
"When you win everyone is always happy and we have to keep going like this," the Belgian added.
"It was good for our confidence. We have done well away from home but we need to win at Old Trafford. It's important for our supporters."