Highlights: Nishikori holds nerve to beat Karlovic in five-set thriller
Nishikori isn't making it easy on himself so far this tournament after losing the first two sets of his first-round contest and then allowing Karlovic to get back into this match.
After coming through his marathon five-setter in three hours and 48 minutes, Nishikori will be hoping for a more straightforward victory against either Philipp Kohlschreiber or Joao Sousa in the next round.
Karlovic produced eight aces in the first set but Nishikori bided his time for the crucial break, which came in the eighth game as a long serve from Karlovic meant he could not escape from 0-40 down - and the world number nine served out to take the opening set.
Nishikori looked to be on course for a routine win when he won a second-set tie-break 8-6 to move 2-0 up, but Karlovic fought back in style. The 39-year-old showed remarkable fitness as he took the third from under Nishikori's nose.
And the Croatian, 10 years Nishikori's senior, took the fourth as he served four consecutive aces to take his tally for the match up to 47 in total against one of the game's best returners of serve.
Ivo Karlovic made Nishikori suffer for his win on Thursday
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Nishikori looked like he had cracked in his fifth service game but he saved three break points before taking a crucial mini-break in the final tie-break.
He stretched his lead to 4-1 in the final-set 10-point tiebreaker only to allow Karlovic to then nudge 7-6 in front - aided by a baseline call which went his way courtesy of Hawkeye.
But a long backhand and long service return by Karlovic allowed Nishikori to retake the lead that he didn't relinquish. After weathering 59 aces from Karlovic, the Japanese held on to win, falling to his knees at the end of a breathless contest.