The Red Devils are flying high at the top of the Premier League, largely thanks to their new £24m signing Van Persie, who has scored a staggering 18 goals in 23 appearances this term.
Meanwhile, Ronaldo remains Madrid’s top scorer with 21 strikes in 21 La Liga appearances, although the former Red Devils star is enduring a mixed season by his own high standards.
“For me the difference will be the form of Cristiano and Van Persie. I think that one of these two players will make the difference,” Van Nistelrooy told Marca.
“Both teams are doing very well. I think Madrid have improved a lot in recent weeks. Taking away the Granada game (1-0 loss) I see a strong team, who played very well against Barca and who show their best in the big games.
“I think the tie will be decided by the smallest details.”
Van Nistelrooy scored 150 goals in 219 appearances for Sir Alex Ferguson’s side before completing a £20m move to Los Blancos in 2006.
The former Netherlands international believes Madrid are the better side, but warned the La Liga champions that United will be clinical if given any chances to score.
“United don’t need many chances to score. Give one to Van Persie and Rooney and it’s going
in. They don’t miss. And the problem is that they always create something,” he added.
“They are a lethal pair.”