Sinner, who defeated Medvedev in the final of the China Open in Beijing at the start of October, ensured history would repeat itself in Vienna with a hard-fought 7-6(7) 4-6 6-3 victory in three hours and five minutes.
The Italian saved two set points in the first before taking it on a tie-break and, after Medvedev had hit back to force a decider, Sinner gained the crucial break of serve in the fourth game, converting his ninth break point.
"It took a lot of mental and physical stuff," said Sinner, as per atptour.com.
"I think we both served very well the first set. I managed somehow to get back on serve when he was a break up, because I felt like he was serving really good. I found a way in the first set.
"Second set, I felt like he was trying to get into the rally a little bit more and I was hustling a little bit. In the third set I tried to step up a little bit. I had a lot of break points, I couldn't use them and then at the end I used them so I'm very happy. Obviously to finish the match, it was really a mental thing, but I'm very happy about how I managed today and very happy for another title."
Meanwhile, in neighbouring Switzerland, Canada's Felix Auger-Aliassime successfully defended his Swiss Indoors Basel title with a 7-6(3) 7-6(5) victory over Hubert Hurkacz.
"I'm definitely back... I let my racquet talk," quipped the Canadian.
"That's always been the motto of my career. I've had the conviction that I can be a top player since I'm a kid, but there were many doubts this year about my performances and why.
"I'm happy that I was able to prove to everybody that I still belong among the best players in the world, that I can play this level. I never doubted it, but it's good to confirm it on the court."