In the 2008 U.S. Open at Torrey Pines South Course, he finished runner-up after losing the first sudden-death hole after an 18-hole playoff to Tiger Woods.

He picked up another victory at the 1993 KMart Greater Greensboro Open, but he then had a long layoff due to a ruptured disk.

On October 9, 2006, it was announced that Mediate would become an on-course reporter for The Golf Channel's 2007 PGA Tour coverage.

At the 2006 Masters, Mediate was in contention to win the event on the final day until he took a septuple-bogey ten on the par-three 12th hole.

His best finish in a major championship was a second-place showing at the 2008 U.S. Open at Torrey Pines South Course.

Mediate earned his first win since 2002 at the 2010 Frys.com Open by beating Bo Van Pelt and Alex Prugh by one shot.

After shooting a 61 in the second round, he claimed victory by two strokes over Bernhard Langer and Tom Pernice Jr. with a birdie at the last hole.

[8] His winning total of 265 (−19) broke the previous record by three and was the first wire-to-wire victory at the event since Jack Nicklaus in 1991.

[9] On September 22, 2019, Mediate won the Sanford International on the PGA Tour Champions in South Dakota.