Five-time champion Roger Federer won in straight sets, while French Open runner-up David Ferrer also was a second- round winner Tuesday at the $3 million Western & Southern Open.
Federer topped Germany's Philipp Kohlschreiber, 6-3, 7-6 (9-7) Tuesday night.
Last year, Federer defeated four-time runner-up Novak Djokovic in the finale to become the first player in the Open Era to win five Cincinnati titles. The only other multiple Cincinnati titlist in this year's field is two- time winner Andy Murray.
The third-seeded Ferrer held off American wild card Ryan Harrison 7-6 (7-5), 3-6, 6-4 in 2 hours, 42 minutes on the hardcourts at the Lindner Family Tennis Center.
Also in the second round, rising Bulgarian Grigor Dimitrov doused oft-injured American Brian Baker 6-3, 6-2 and Frenchman Julien Benneteau downed Czech Radek Stepanek, 6-2, 5-7, 7-6 (7-4).
Ninth-seeded Swiss slugger Stan Wawrinka bested Italian Andreas Seppi 6-3, 6-4 in first-round play.
In other opening-round action involving seeds, Spanish left-hander Feliciano Lopez upended No. 12 Japanese Kei Nishikori 6-4, 7-6 (7-4), No. 11 German Tommy Haas handled South African Kevin Anderson 6-4, 6-4 and rising Canadian Vasek Pospisil upset No. 15 Frenchman Gilles Simon 6-3, 1-1, retired. Pospisil was a semifinalist at last week's Rogers Cup Masters event in Montreal.
Canadian Milos Raonic, the 12th seed, defeated American wild card Jack Sock, 3-6, 6-4, 6-3.
Last week's Canadian Masters runner-up Raonic became the first-ever Canadian to reach the ATP's top 10 this week.
Also in the first round, American John Isner fired 17 aces in topping German Florian Mayer 6-3, 6-4, former top-five Russian Nikolay Davydenko beat Frenchman Benoit Paire 7-6 (10-8), 6-3, Russian Mikhail Youzhny erased Latvian Ernests Gulbis 7-5, 6-3, and Finland's Jarkko Nieminen dismissed French qualifier Edouard Roger-Vasselin 6-3, 6-4. Youzhny's second-round opponent will be the Wimbledon champion Murray.
Additional opening-round wins came for Spanish veteran Tommy Robredo and German qualifier Benjamin Becker, who is rewarded with a second-round match against last week's Montreal Masters champ Rafael Nadal.
The 2013 Cincinnati champ will collect $583,800.
This is the last Masters 1000 event before the U.S. Open, which will commence August 26 in New York.