He arrived at Melbourne Park a year ago having taken off the previous six months to rest his injured elbow and went on to lose in the fourth round, after which he underwent surgery.
The second set was tighter as Osaka uncharacteristically struggled on serve, double faulting as Zidansek went up a break.
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.
Ivo, the oldest player with a win at the Australian Open since great Ken Rosewall in 1978, did his best to stay in touch with much younger and better-ranked rival, blasting 59 aces and losing serve only once in the entire match!
Ivo Karlovic has broken plenty of serving records in his time but it was as a result of his age that the 39-year-old Croatian made further entries in the sport's history books here at Australian Open 2019 on Tuesday.
The 16th-seeded Raonic, the Wimbledon runner-up in 2016, hit 39 aces in the 4-hour, 2-minute thriller.
He launched his campaign for a seventh with a 6-3, 6-2, 6-2 victory over Mitchell Krueger, a 25-year-old American making his debut in the main draw here. He was playing very well, better than I thought, I have to say.
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And he has suggested that, like in both games against Blackburn , he will play his reserves in the FA Cup going forward. He continued: "That is going to help us".
But Nishikori stepped it up, winning the last three points and sparking chants of "Nishi-kori, Nishi-kori" from a section of Japanese fans at Margaret Court Arena. Two from 30-30 in the 10th game and then another four to close after breaking Nishikori's serve to close out the fourth set.
The fourth-seeded Osaka recovered a service break in the second set and, at 4-4, she broke Zidansek's service to love. He was smiling, but no one knew for sure if he was offended or was just joking.
"I had to reload in the fifth", he said. In September, she defeated 23-time major champion Serena Williams at the U.S. Open to become the first Japanese player to win a Grand Slam. "Again, if I take some distance, see a little bit everything I've done the last few months to get at that level, I'm quite happy - I'm looking forward for the rest of the year". But then, in the seventh game, Nishikori got himself into a 0-40 hole, and when Majchrzak blasted a backhand victor on his third game point, the recent Brisbane champion again found himself behind.
Osaka was in no mood to hang around after rain delayed the start of play as the roof on Margaret Court Arena was closed. Tsonga, who has had his own fitness issues in recent years and is now ranked No 177 in the world, beat Martin Klizan 6-4, 6-4, 7-6.
Hsieh Su-wei also advanced by beating Laura Siegemund 6-3, 6-4. Other women through included Italy's Camila Giorgi, who plays Pliskova next, and China's impressive 21st seed Wang Qiang.
"Fourth set was really tough I lost four easy games".