Djokovic won previous year in the quarter-final at Wimbledon 6-3, 3-6, 6-2, 6-2 and the US Open semi-final 6-3, 6-4, 6-2 on his way to lifting both titles.
He went five sets again in his controversial fourth-round clash against Pablo Carreno Busta, which took five hours and five minutes.
Nishikori had a medical time-out between sets, with the trainer working on a right thigh problem.
The world number one said: "I love to battle, especially against Kei, we've played so many matches. I hope it's not too serious and he has a speedy recovery", he added. "Im sorry to everybody for not having a full match but thank you for showing up".
"This is exactly what the doctor ordered for me, as the saying is", Djokovic said.
"I've had plenty of matches so far this year and I am in another semifinal and I will do everything to get ready for that one".
According to the statistics of provided by the tournament's official website, the 29-year-old Japanese player had spent a total of 13 hours and 47 minutes to reach the quarterfinals since the opening match of the 2019 Australian Open, which has $44.5 million in prize money up for grabs and runs between January 14 and 27.
Before those matches though, we have the first two quarter-finals of the event take place, with Roberto Bautista-Agut facing Roger Federer's conqueror, Stefanos Tsitsipas, in the first match on the schedule.
In the Friday night semifinal, Djokovic will meet Lucas Pouille who chopped down Milos Raonic 7-6 (4), 6-3, 6-7 (2), 6-4. Following these matches, it's Djokovic v Nishikori and Raonic v Pouille on Wednesday.
He broke the resistance of Nishikori instantly, pouncing on his first break point opportunity, before securing the double break in the sixth game of the set.
"I'm still leading two sets to one, so I don't have to panic".
"But then boom, he could see Medvedev was getting a little bit slow, he'd done so much running and he's a tall lanky kid who stands a long way back and Djokovic went right, that's it, I'm going to keep moving you then boom, went straight through".
Djokovic offered his condolences, but his immediate focus nevertheless will be on his 34th major semifinal.
"I'm expecting him to come out and be confident and I'm looking forward to it".
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