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Isner won 7-6 (7/4), 6-2, 7-6 (8/6) against Frenchman Mahut in a contest every bit as low-key as their 11-hour epic last year was dramatic.
The first game of the match lasted less than a minute and although there were two tiebreaks the clash never threatened to live up to last year's three-day marathon, by far the longest match in tennis history.
Isner took control by winning the first-set tiebreak and Frenchman Mahut never looked like fighting back in a subdued atmosphere on a windy Court Three.
"The phenomenon that was created around last year's match has been difficult for the two of us to tackle," 94th-ranked Mahut told a news conference.
"He played better than me today. The atmosphere was not as huge as I was waiting for," added the Frenchman, who despite his dejected demeanour still found room for humour.
"I'm sure you're all disappointed about today," he joked.
Inseparable through a fifth set which ended 70-68 and lasted over eight hours 12 months ago, the only thing the friends had in common a year later was a pair of identical shoes as the giant 47th-ranked Isner took control of the match.
The pair embraced warmly at the net and exchanged kind words after the match.
"'Hey, buddy. I want to see you in the second week of this event,' he told me," Isner said.
"Thank you I replied," added the American, who lost his second-round encounter in 74 minutes last year due to the inevitable onset of fatigue.
"I'm just really thrilled to have won that third set, because if I lose that third set, then chances are we don't finish and our match goes to another second day."
After Mahut trudged away, Isner had to battle through hoards of autograph hunters though he lifted his head briefly when he heard a cry from one familiar voice.
"Where were you?," Isner asked Mohamed Lahyani, the chair umpire at last year's match who had come to congratulate the American.
Results from the second day of the Wimbledon on Tuesday (x denotes seeding):
Men
First Round
Juan Martin Del Potro (ARG x24) bt Flavio Cipolla (ITA) 6-1, 6-4, 6-3
Olivier Rochus (BEL) bt Kenny De Schepper (FRA) 6-7 (6/8), 3-6, 6-3, 6-1, 6-4
Gilles Simon (FRA x15) bt Edouard Roger-Vasselin (FRA) 4-6, 6-4, 6-3, 7-6 (7/3)
Robin Haase (NED) bt Pere Riba (ESP) 6-4, 6-4, 6-4
Fernando Verdasco (ESP x21) bt Radek Stepanek (CZE) 2-6, 4-6, 6-3, 7-6 (8/6), 9-7
Juan Ignacio Chela (ARG x25) bt Marinko Matosevic (AUS) 6-4, 6-4, 6-7 (6/8), 6-2
Tobias Kamke (GER) bt Blaz Kavcic (SLO) 6-3, 7-6 (7/4), 5-7, 6-1
Sergiy Stakhovsky (UKR) bt Daniel Cox (GBR) 6-2, 6-4, 6-4
Ivan Ljubicic (CRO) bt Marin Cilic (CRO x27) 7-6 (7/2), 3-6, 6-3, 6-4
Lukasz Kubot (POL) bt Arnaud Clement (FRA) 6-4, 6-2, 3-6, 5-7, 6-4
Ivo Karlovic (CRO) bt Janko Tipsarevic (SRB x23) 7-5, 3-1 - retired
Victor Hanescu (ROM) bt Jaroslav Pospisil (CZE) 6-4, 6-3, 6-2
Andy Roddick (USA x8) bt Andreas Beck (GER) 6-4, 7-6 (8/6), 6-3
David Ferrer (ESP x7) bt Benoit Paire (FRA) 6-4, 6-4, 6-4
Ryan Harrison (USA) bt Ivan Dodig (CRO) 7-6 (7/5), 6-0, 7-5
Karol Beck (SVK) bt Carlos Berlocq (ARG) 4-6, 7-6 (8/6), 4-6, 6-2, 6-4
Guillermo Garcia-Lopez (ESP x26) bt Andrey Golubev (KAZ) 6-3, 6-3, 0-0 abandon
Fernando Gonzalez (CHI) bt Oleksandr Dolgopolov (UKR x22) 6-3, 6-7 (6/8), 7-6 (7/3), 6-4
Rik De Voest (RSA) bt Ruben Ramirez Hidalgo (ESP) 6-2, 6-3, 6-2
Jo-Wilfried Tsonga (FRA x12) bt Go Soeda (JPN) 6-3, 7-6 (7/4), 6-2
Nicolas Almagro (ESP x16) bt Jarkko Nieminen (FIN) 6-7 (5/7), 6-3, 6-4, 6-4
John Isner (USA) bt Nicolas Mahut (FRA) 7-6 (7/4), 6-2, 7-6 (8/6)
Somdev Devvarman (IND) bt Denis Gremelmayr (GER) 6-4, 4-2 - retired
Mikhail Youzhny (RUS x18) bt Juan Monaco (ARG) 4-6, 6-2, 6-2, 4-6, 6-4
David Nalbandian (ARG x28) bt Julian Reister (GER) 7-5, 6-2, 6-3
Adrian Mannarino (FRA) bt Conor Niland (EIR) 4-6, 6-4, 7-6 (9/7), 3-6, 6-4
Roger Federer (SUI x3) bt Mikhail Kukushkin (KAZ) 7-6 (7/2), 6-4, 6-2
Robin Soderling (SWE x5) bt Philipp Petzschner (GER) 6-4, 6-4, 2-6, 7-6 (7/5)
Lleyton Hewitt (AUS) bt Kei Nishikori (JPN) 6-1, 7-6 (7/4), 6-7 (7/9), 6-3
Igor Andreev (RUS) bt Teimuraz Gabashvili (RUS) 6-4, 7-6 (7/5), 6-7 (4/7), 4-6, 6-3
Bernard Tomic (AUS) bt Nikolay Davydenko (RUS x29) 7-5, 6-3, 7-5
Florian Mayer (GER x20) bt Daniel Evans (GBR) 7-6 (7/5), 7-6 (7/1), 3-6, 6-4
Xavier Malisse (BEL) bt Mischa Zverev (GER) 6-2, 6-3, 6-2
Jurgen Melzer (AUT x11) bt Alejandro Falla (COL) 3-6, 7-6 (7/5), 6-2, 6-2
Viktor Troicki (SRB x13) bt Maximo Gonzalez (ARG) 3-6, 6-0, 7-6 (7/3), 6-3
Lu Yen-Hsun (TPE) bt Tommy Robredo (ESP) 6-4, 6-4, 6-1
Ricardo Mello (BRA) bt Frank Dancevic (CAN) 3-6, 3-6, 6-4, 7-6 (8/6), 6-2
Michael Llodra (FRA x19) bt James Ward (GBR) 6-3, 7-6 (7/4), 6-3
Marcos Baghdatis (CYP x32) bt James Blake (USA) 6-4, 6-2, 6-7 (5/7), 4-6, 6-4
Andreas Seppi (ITA) bt Albert Montanes (ESP) 6-4, 6-4, 7-5
Novak Djokovic (SRB x2) bt Jeremy Chardy (FRA) 6-4, 6-1, 6-1
Women
First Round
Caroline Wozniacki (DEN x1) bt Arantxa Parra Santonja (ESP) 6-2, 6-1
Virginie Razzano (FRA) bt Sania Mirza (IND) 7-6 (7/4), 2-6, 6-3
Melinda Czink (HUN) bt Samantha Stosur (AUS x10) 6-3, 6-4
Anastasiya Yakimova (BLR) bt Sofia Arvidsson (SWE) 4-6, 6-2, 6-1
Elena Baltacha (GBR) bt Mona Barthel (GER) 6-2, 6-4
Shuai Peng (CHN x20) bt Kirsten Flipkens (BEL) 6-0, 6-4
Klara Zakopalova (CZE) bt Emily Webley-Smith (GBR) 6-3, 5-7, 8-6
Maria Sharapova (RUS x5) bt Anna Chakvetadze (RUS) 6-2, 6-1
Li Na (CHN x3) bt Alla Kudryavtseva (RUS) 6-3, 6-3
Marion Bartoli (FRA x9) bt Kristyna Pliskova (CZE) 6-0, 6-2
Maria Kirilenko (RUS x26) bt Alberta Brianti (ITA) 6-2, 6-1
Simona Halep (ROM) bt Bojana Jovanovski (SRB) 6-1, 6-2
Serena Williams (USA x7) bt Aravane Rezai (FRA) 6-3, 3-6, 6-1
Barbora Zahlavova Strycova (CZE) bt Aleksandra Wozniak (CAN) 7-6 (9/7), 6-4
Tamira Paszek (AUT) bt Ayumi Morita (JPN) 5-7, 6-3, 6-0
Stephanie Dubois (CAN) bt Irina Falconi (USA) 6-2, 6-2
Andrea Petkovic (GER x11) bt Stephanie Foretz (FRA) 6-3, 6-4
Anastasia Pavlyuchenkova (RUS x14) bt Lesya Tsurenko (UKR) 6-4, 7-6 (7/3)
Nadia Petrova (RUS) bt Vesna Dolents (RUS) 6-3, 6-4
Kateryna Bondarenko (UKR) bt Alize Cornet (FRA) 7-5, 6-2
Daniela Hantuchova (SVK x25) bt Vitalia Diatchenko (RUS) 4-6, 7-6 (7/5), 6-3
Marina Erakovic (NZL) bt Kai-Chen Chang (TPE) 6-4, 6-2
Iveta Benesova (CZE) bt Sandra Zahlavova (CZE) 3-6, 6-3, 7-6
Victoria Azarenka (BLR x4) bt Magdalna Rybarikova (SVK) 6-4, 3-2 -retired
Petra Kvitova (CZE x8) bt Alexa Glatch (USA) 6-2, 6-2
Anne Keothavong (GBR) bt Naomi Broady (GBR) 6-2, 6-4
Rebecca Marino (CAN) bt Patricia Mayr (AUT) 6-3, 7-6 (7/5)
Roberta Vinci (ITA x29) bt Vera Dushevina (RUS) 7-5, 6-2
Maria Jose Martinez (ESP) bt Jelena Jankovic (SRB x15) 5-7, 6-4, 6-3
Tsvetana Pironkova (BUL x32) bt Camila Giorgi (ITA) 6-2, 6-1
Petra Martic (CRO) bt Vania King (USA) 5-7, 6-2, 6-2
