Van Nistelrooy had taken charge of United on an interim basis during the four matches since Erik ten Hag's sacking and has impressed with a number of good results to keep the team’s European chances alive.
However, he has now left the club as Ruben Amorim and his staff come in and look to switch things up at the club once again, leaving no room for Van Nistelrooy despite calls from fans for him to stay.
The Dutchman has taken to social media to wave goodbye to fans with many predicting he will find a managerial job elsewhere after looking comfortable in the hot seat at United.
“To everyone at Manchester United Football Club, in particular the backroom staff, the players and the fans.
"I want to thank you from the bottom of my heart for your incredible efforts and support. It has been a privilege and honour to represent the club as a player, coach and manager, and I will always cherish the memories we have shared together.
"Man Utd will always have a special place in my heart, and I hope there are many more glory days at Old Trafford very soon - not only because I want the club to do well, but because you all deserve it! All the best and take care, Ruud."