Japan's Kei Nishikori bowed out of Wimbledon on Wednesday after losing to Novak Djokovic of Serbia 6-3, 3-6, 6-2, 6-2 in the quarterfinals of the grass-court major.

The loss marks the end of world No. 28 Nishikori's most successful ever Wimbledon appearance, having reached the final eight for the first time in his career.

Nishikori also missed out in his bid to become the first Japanese since Jiro Sato in 1933 to advance to the men's singles semifinals at Wimbledon.

"I didn't play badly but in the end there was something lacking, I wasn't able to beat him." said Nishikori. "I need to find that something. I had a couple of chances, but he played a good full match."

Nishikori, who returned from a five-month wrist injury layoff in January, was playing with painkillers after getting his right elbow treated during his fourth-round match Monday.

Having broken Nishikori early in the first set, 21st-ranked Djokovic went on to surrender his subsequent serve with a double fault at break point, and Nishikori served to draw even at 3-3.

However, he later handed Djokovic another break with a wide backhand, allowing Djokovic to serve out and take a comfortable first set.

Coming back in the second set, Nishikori held his serve in a long first game and went on to break Djokovic after the Serb received a code violation for racket abuse, serving out to draw level at one set apiece.

He then failed to convert three crucial break opportunities on Djokovic's serve at 2-2 in the third set, giving away the game and then his next two serves to hand the Serb the set.

After breaking Djokovic's first serve to get off to a promising start in the fourth set, Nishikori was immediately relinquished of his lead as Djokovic broke back once and then again. A final break clinched with a forehand winner, and the match was lost.

"He was playing very deep, he was going both sides with his back and then his forehand too...he was making me run all the time. Honestly, it's not easy playing Novak," Nishikori said.

"Today I had a tough opponent, a big challenge," said Djokovic. "We were even until the third set when I managed to step up a gear and end up this match really well."

Victory always appeared likely to be a tall order for Nishikori, who has lost to three-time Wimbledon champion Djokovic in 13 of 15 previous matches. He last beat him at the semifinals of the U.S. Open in 2014, where he reached the final in his best ever performance at a grand slam.

"It gives me confidence that I was able to play good tennis on grass," Nishikori said. "I'm frustrated to lose today, but these two weeks have helped me going forward."

"I want to use today's result as a springboard from which to aim for a place in the final."