The 44-year-old legendary Dutchman arrived at Old Trafford in 2001 after United splashed out a then-British record transfer fee of £19m.
Sir Alex Ferguson's desire to land Van Nistelrooy from Dutch side PSV Eindhoven was highlighted in the United hero's remarkable goalscoring ability.
During his incredible five seasons in England, Van Nistelrooy scored an impressive 150 times in 219 matches for United.
While his relationship with Ferguson fractured ahead of his departure to Real Madrid in 2006, Van Nistelrooy left a lasting impression in the Premier League and on United fans.
Now, ESPN named the former Netherlands international as United's best striker of the Premier League era.
Mark Ogden compiled the rankings and hailed Van Nistelrooy as an "absolute cold-hearted goalscorer."
The ESPN writer believes that the United legend would have smashed Sir Bobby Charlton's former all-time goalscoring record for the club, setting a "mark that even Rooney couldn't have [over]taken."
Ogden explained: "Van Nistelrooy was just an absolute cold-hearted goalscorer -- 150 goals in 219 games.
"Had his relationship with Sir Alex Ferguson not deteriorated as it did, I think he would have gone on to become the all-time top scorer at United.
"I think he would have gone past Sir Bobby Charlton and set a mark that even Rooney couldn't have [over]taken because he was just... he would never pass, but I don't want my strikers -- my best star striker -- to pass.
"If he has a sight on goal, take a shot and go -- and that's what Van Nistelrooy did. He was freakishly good.
"His strike rate was just incredible. He scored at 0.66 -- that's his strike ratio. It's just, for me, outstanding [...].
"We didn't see the best of him, maybe, because his time at United ended a bit too quickly."
Posted below are ESPN's top five picks for United's best Premier League strikers of all time.
5. Zlatan Ibrahimovic
4. Eric Cantona
3. Wayne Rooney
2. Robin van Persie
1. Ruud van Nistelrooy
Featured Image Credit: PA
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