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Nadal and Nalbandian rallied on Tuesday to win their opening doubles match 6-3, 3-6, 11-9 over the Spanish team of Pablo Andujar and Guillermo Garcia Lopez.
The team withdrew from the doubles competition before their scheduled Wednesday night match against Argentina's Horacio Zeballos and Austria's Oliver Marach.
Last Sunday, Zeballos upset Nadal 6-7, 7-6, 6-4 in the final of a clay-court event in Viña del Mar, Chile, Nadal's first tournament since last year's Wimbledon.
Nadal and Nalbandian said they wanted to rest and stay fresh for the singles competition.
Nadal, who is the top seed and favorite to win the tournament, plays Brazil's Joao Souza on Thursday.
Nalbandian, who advanced to the quarterfinals with a 7-5, 5-7, 6-3 win against Chile's Jorge Aguilar, will play countryman Guido Pella on Thursday.
"It's a shame that Rafa and I had to pull out of the doubles. It would have been wonderful to once again play before these fans," Nalbandian said.
A packed crowd of 9,000 spectators gathered at Sao Paulo's Ibirapuera arena Tuesday evening to watch Nadal in his second tournament back after seven months out of action due to a knee injury and illness.
They nearly went home disappointed when Nadal and Nalbandian, a former world No. 3, trailed 9-7 in the 10-point tiebreaker. But the Spanish-Argentine duo came alive with clutch play to save two match points and then go on to claim the victory.
Nadal went off the ATP tour after suffering a shock second-round exit at last year's Wimbledon at the hands of unheralded Czech Lukas Rosol, considered one of the biggest upsets in the history of that prestigious tournament.
Nadal had planned to return to action in late December in Abu Dhabi, but a stomach virus forced him to withdraw from that exhibition tournament and he also pulled out of the recently concluded Australian Open.