Manu, who scored 19 of his 24 points in the second half, made his first appearance of the season with a goal and assist on Wednesday against the Chicago Bulls, which dropped a 4-1 decision to the Miami Heat.
It was his second game in less than a week, and he was on the court for the first time since mid-October.
Ginobil was the last player to play in every game this season before being suspended for two games for his role in the Boston Marathon bombings last month.
Ginobil scored the only points of the first half for the Heat, which was led by Hassan Whiteside and LeBron James.
It looked like the Heat had the momentum when Ginobill finished with five points, five rebounds and four assists.
He was fouled with 15 seconds remaining in the third quarter and was called for a technical foul.
But Miami held on to beat the Heat 4-2 in a game that had been decided by six points.
Ginoby was fined $12,000 for his actions on the play, but Heat coach Erik Spoelstra said that is nothing compared to what he has seen from Ginobilic in previous games.
Spoelstras words were that it is not fair to him to say Manu is a liability.
The Heat will need him to be on the floor for the rest of the games to make a difference.