Pettitte -- who has not pitched in a big league game since July 18 with a strained left groin -- hurled five innings in a rehab start Tuesday for Double-A Trenton at Altoona, allowing two runs and six hits over 67 pitches.
The veteran left-hander will throw a side session Thursday, the final stumbling block to his return, but that is expected to be a formality. Girardi said that Pettitte would be ready to throw about 90 pitches against the Orioles.
"I want to see how he feels tomorrow after his side [session]," Girardi said. "Right now, all indications are that he feels good. That's really important; it'd be frustrating if he didn't, for him and all of us."
With Pettitte's return, Girardi said that A.J. Burnett will pitch Friday and CC Sabathia will go Saturday at Camden Yards. Javier Vazquez will be bumped to the bullpen for the third time this season, unless he is needed as an emergency starter should Pettitte not be able to go.