The win was Safin's first in three meetings with Ginepri, who won the tournament at Indianapolis last week, but the two had not played in four years. Safin won just one point in the final three games of the opening set. He took control of the second set by winning the first three games and repeated that in the third set while breaking Ginepri's serve twice.
"Robby is playing really well, coming from a title last week. He is a tough player. It was a well-played match from both of us," Safin said. "I was able to go up a break in the beginning of the second set and that helped me to turn the match around."
The 6-foot-9 Isner, who had mononucleosis and was absent from the ATP Tour for three months, returned to action last week at Indianapolis, where he lost to eventual champion Ginepri in the semifinals.
Isner said he was "maybe a little bit tired today" after Tuesday's 2-hour, 5-minute win that came on the heels of four matches at Indianapolis.
"I've just got to get in a little better shape, match shape," he said. "When you take a month off and don't do anything you lose a lot."
There were just two service breaks in the match, both in the second set. Becker got the first, to take a 3-1 lead, then had what he called "a 5-minute mental letdown" and lost his serve.
That was the only one of eight break points converted by Isner, but it got him back on serve and eventually into the tiebreaker, where he won the final four points.
No. 5 seed Igor Kunitsyn got his title bid under way with a 7-5, 6-2 win over qualifier Somdev Devvarman, an NCAA singles champion while at Virginia. Sixth-seed Sam Querrey beat Denis Istomin 6-2, 6-0.
Ernests Gulbis beat Yen-Hsun Lu of Tapei, 7-5, 6-2; qualifier Ryan Sweeting topped Taylor Dent, 6-4, 2-6, 6-3, in a matchup of Americans; and qualifier Carsten Ball eliminated Marc Gicquel 6-2, 7-6 (6) in other early matches.