
According to Real, the operation - carried out in Amsterdam by ankle specialist doctor Van Dijk - was a success.
Van Nistelrooy, 31, will now be out of action for around six weeks, which means that his participation for Holland in the European Championship finals could be in doubts.
He has not played since 24 February because of acute and painful sinovitis in the right ankle. Without him, Real have struggled to score goals, and were eliminated from the Champions League by AS Roma.
Van Nistelrooy top-scored with 25 goals in La Liga last season, and has scored 12 goals in 21 games this term.
His injury will be an opportunity for young striker Roberto Soldado, who has hardly got off the bench since returning in July from a season on loan at Osasuna.
The only consolation for Real is that historic rivals Barcelona - who are seven points behind them in La Liga - are undergoing an even more severe injury crisis, with the likes of Lionel Messi, Ronaldinho and Deco all out.