17 year-old Vaidisova, ranked 12 in the world, found it difficult to play against Safarova, her friend and countrywoman.
"I've had some tough matches, a compatriot in the quarter-finals is always tough but I'm so happy I'm through, it feels great," Vaidisova said.
"It's great for Czech tennis to have two quarter-finalists, one in the semis. Of course you don't want to play your friend but I'm just happy I got through it."
It seemed Safarova's fourth round triumph was her personal final as she looked a shadow of the player whose aggression left Mauresmo reeling earlier in the week, appearing tentative and reluctant to attack the net the way she did against the title holder.
"I knew it would be tough because she has a similar game to me, fast, flat," said Safarova.
"I knew if I was to win I would have to serve well and that was the difference, she was serving so well."
A semi-finalist at Roland Garros last year, Vaidisova raced through the first set after breaking twice early, and then used her big match experience to close out the match in one hour and 11 minutes.
Serena scrapes through
Later on centre court the unseeded Serena Williams fought hard to come from behind in an epic three-setter against 16th seed Shahar Peer of Israel after dropping the first set 3-6.
Tough work: Serena Williams came from one
set down to beat Shahar Peer [AFP]
"I am the ultimate competitor," declared Williams, the Australian Open champion in 2003 and 2005.
"I wasn't playing my best tennis, I'm excited I was able to come through, I wasn't the best I can be today," Willlams added.
19 year-old Peer, who fulfils her mandatory military service with the Israeli army when not on the tennis tour, served for the match in the third set but couldn’t land the killer blow as Williams' experience shone through.
The epic match may take its toll however, as the 25 year-old American was on court for two hours and 34 minutes - more than twice as long as her semi-final opponent Vaidisova.