Updated

Rafael Nadal won the latest encounter with Roger Federer, battling back from a set down to beat his adversary Friday night in the quarterfinals at the $3 million Western & Southern Open, a hardcourt ATP Masters 1000 event.

Nadal ran his record on hardcourts this season to 13-0 with a 5-7, 6-4, 6-3 triumph at the Lindner Family Tennis Center. The fourth-seeded Spaniard improved his head-to-head record against Federer, the reigning champ and a five-time Cincy titlist, to 21-10.

The fifth-seeded Swiss star followed up a late break with a cross-court backhand to take the opening set.

The second set unfolded almost the same way, with the combatants remaining on serve until a misfired shot by Federer set up a second set point for Nadal, who sent a sizzling forehand past Federer for his first break.

Nadal, last week's Masters champion in Montreal, broke Federer again while storming out to a 3-0 lead in the third set. On his fifth match point, Nadal fired a forehand that was ruled to have clipped the left sideline. Federer opted not to challenge what a replay showed was the wrong call as the ball landed just outside the line.

Federer, who fell to 1-6 this year against Top 10 opponents, wasn't the lone Grand Slam champion to lose Friday.

American crowd favorite John Isner toppled world No. 1 star Novak Djokovic, while Tomas Berdych dismissed Wimbledon champion Andy Murray.

The unseeded Isner knocked out the four-time Cincinnati runner-up Djokovic in three sets, 7-6 (7-5), 3-6, 7-5. The tight match was decided when the towering American broke the Serbian stalwart in the final game of the bout.

Isner, who was a hardcourt runner-up in Washington, D.C., two weeks ago, is now 2-3 lifetime against Djokovic, with the other victory coming at a Masters event in Indian Wells, Calif., last season.

Djokovic lost to Federer in last year's marquee finale.

This is the only Masters tournament that Djokovic has failed to win. He was the runner-up four of the last five years.

A sixth-seeded Berdych, meanwhile, bounced the second-seeded Murray in straight sets, 6-3, 6-4, on Day 6. Murray has now failed to get past the quarterfinals at both of his events since capturing his first Wimbledon title last month. He was a third-round loser in Montreal last week.

The reigning Wimbledon and U.S. Open champion Murray is a two-time Cincy titlist (2008, 2011).

Seventh-seeded former U.S. Open champ Juan Martin del Potro held off oft- injured Russian veteran Dmitry Tursunov, 6-4, 3-6, 6-1. The 6-foot-7 Argentine slugger del Potro beat Isner in the recent D.C. finale and will face the 6- foot-9 American once again in Saturday's semifinals.

Nadal and Berdych will clash in the other semifinal.

This is the last Masters tournament before the U.S. Open, which will commence August 26 in New York.

The 2013 Cincinnati champ will collect $583,800.