Vaidisova and Safina earned their first berths in a Grand Slam quarterfinal.
Top-ranked Roger Federer, seeking his fourth consecutive major title, advanced to the quarterfinals by beating No. 20 Tomas Berdych, 6-3, 6-2, 6-3. Croats Ivan Ljubicic and Mario Ancic also won, as did two-time champion Justine Henin-Hardenne, two-time runner-up Kim Clijsters, and former US Open champion Svetlana Kuznetsova on the women's side.
Henin-Hardenne, seeded fifth, beat 2004 champion Anastasia Myskina, 6-1, 6-4.
No. 10 Gaston Gaudio, the 2004 champion, was eliminated by No. 6 Nikolay Davydenko, 6-3, 6-4, 3-6, 6-3. Davydenko will next play No. 3 David Nalbandian, who swept qualifier Martin Vassallo Arguello, 6-4, 6-4, 6-4.
Sharapova, seeded fourth, said rustiness following a recent injury layoff contributed to her unraveling.
``You're thinking left and right, and you don't know what you're doing," Sharapova said. ``You go into a different world, and you make dumb decisions."
She failed to convert two set points in the opening set, then rallied but couldn't close out the victory. She was twice broken serving for the match, hitting errant forehands on three consecutive points to lose serve for 5-all.
Safina controlled the rallies in the final two games, keeping her Russian compatriot on the move and on her heels.
``I took everything in my hands," said Safina, seeded 14th. ``Before, she was dictating and I had always to run from corner to corner. I said, `OK, now I'll try to make her run.' I started to be more aggressive."
The tournament was the first since April 1 for Sharapova, who withdrew from two events leading to Roland Garros because of a right ankle injury.
``I haven't played a lot of matches in the past weeks and don't feel like I'm match-tough enough," she said. ``Of course, I'm disappointed, but I didn't think I would be playing my best tennis here."
Federer next meets 12th-seeded Ancic, who reached the quarterfinals by beating No. 7 Tommy Robredo, 6-4, 4-6, 2-6, 6-4, 7-5. Ancic vomited in the fifth set and interrupted a game to receive treatment for cramps.
