Federer earned $1 million, the richest winner's checks in the tournament's history. Isner earned $500,000.
Federer improved to 39-2 since last year's U.S. Open, with his only losses to No. 2 Rafael Nadal in the semifinals of the Australian Open and the 11th-ranked Isner, who won on the Swiss star's home turf last month.
"This year I decided I wanted to play a bit more," Federer said. "If things went great, I knew I could be on a great run coming into Indian Wells and Miami. That's exactly what happened. I'm a bit surprised it's all gone that well."
Federer, ranked third, avenged both those defeats in consecutive days at Indian Wells, putting away Nadal in the rain-delayed semifinals Saturday and then then Isner in a final delayed 12 minutes in the first set by rain drops. He battled a cold most of the two-week tournament, and felt especially sick during the first three days.
"I was able to come through and so convincingly at the end is amazing," he said. "I've really played amazing these last three matches in particular. I couldn't be more happy. They were really great wins."
Federer's victory tied him with Nadal for most ATP World Tour Masters 1000 career titles at 19, cheered on by friends that included musicians Gwen Stefani and her husband Gavin Rossdale, and Vogue editor in chief Anna Wintour. Federer won three straight titles here from 2004-06 and his fourth snapped a tie with Jimmy Connors and Michael Chang.
"What surprises me is that I've actually won this again after all this time," Federer said, "and particularly this year where I was struggling and hurting a lot at the beginning of the year."
Isner had a breakthrough two weeks in the desert, beating top-ranked Novak Djokovic in the semifinals to reach his first Masters 1000 final. That assured him of entering the top 10 for the first time at No. 10 when the latest rankings come out Monday.
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"I'm going to remember this one for a long time, so getting into the top 10 is nice," Isner said. "The hard thing now is staying inside of the top 10. That's what I've got to work on."
The big-serving American actually had three fewer aces than Federer's seven, with his fastest serve clocked at 135 mph, slower than the 135-143 mph he was hitting against Djokovic.
"Thank God at times maybe he didn't hit the big one at 140 something down the T," Federer said.
Federer broke him on Isner's netted backhand volley to go up 4-3 in the second. He closed out the match on Isner's forehand that landed in the net.
"I served pretty well," Isner said. "I don't think I lost the match because I didn't serve as well. He was on top of me and his forehand was way too good."
In the tiebreaker, Isner was serving at 7-all when Federer managed a backhand lob over his 6-foot-9 opponent and Isner let it go, with the ball landing on the baseline. Federer won that point and the next to take the set.
"A little bit unlucky there," Isner said. "I'm not complaining. I had a lot of things go my way this week."
Information from The Associated Press was used in this report.
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