"This week was one of the best for me," Nishikori, who beat Denis Kudla, Grigor Dimitrov and Jeremy Chardy this week, said.
"I've never had a week like this to start the season, so it gives me a lot of confidence."
World number nine Nishikori started slowly, trailing 3-0 in the opening set but responded in typically determined fashion to win six of the next seven games for an early advantage.
Medvedev saved four break points to take a 3-2 lead in the second set before dragging the match into a decider but his opponent, who lost their previous meeting in last year's Tokyo final, was not to be denied again.
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Breaking Medvedev for a 3-1 lead in the third set, Nishikori held firm to seal the match in a little more than two hours for his first trophy since winning in Memphis in February 2016.
"Great final today, I lost to him last year in the final in Japan, so I'm happy to get revenge today," Nishikori added.
"I'm really happy that finally I've won this title, it's been like seven or eight times at this tournament."
Earlier, former world number one Karolina Pliskova battled back from a set and a break down to beat Lesia Tsurenko 4-6 7-5 6-2 and win the women's title for the second time.
Tsurenko served for the match at 5-3 in the second set but the tall Czech drew on all her experience to overcome her dogged opponent and regain the title she won at the Queensland Tennis Centre two years ago.
The Ukrainian took an injury time out after rolling her ankle while being broken in the first game of the third set and was powerless to prevent the world number eight from storming to her 12th career title.
"I think everything was against me today... I felt there is no chance I can win. I felt so far away from playing good tennis tonight," Pliskova, who needed a pep talk from coach Rennae Stubbs to regain composure, said.
"Rennae said 'I am absolutely sure you can win this match,' which gave me some confidence and belief that I can do it.
"I just tried to change the things around a little bit and believed I was going to get a chance... I felt I was getting better with the time."
Victory meant Pliskova joined Victoria Azarenka (2009, 2016) and Serena Williams (2013-14) as the third woman to win the Premier event twice.
(Writing by Nick Mulvenney and Shrivathsa Sridhar, editing by John O'Brien and Christian Radnedge)
