The same animal had ripped the flesh off a zookeeper's arm just before Christmas 2006.
An investigation of that incident by the California Division of Occupational Safety and Health blamed the zoo, which strengthened the security of the pen where big cats are kept.
The zoo's director of animal care and conservation, Robert Jenkins, could not explain how the 136kg tiger escaped.
The tiger's enclosure is surrounded by a 15ft moat and 20ft-high walls and the tiger did not leave through an open door, he said.
"There was no way out through the door," Jenkins said. "The animal appears to have climbed or otherwise leaped out of the enclosure."
The two injured men, aged 19 and 23, were in a stable condition on Wednesday at San Francisco General Hospital after surgery to clean and close their wounds, said Rochelle Dicker, their surgeon at the hospital.
They suffered deep bites and claw cuts on their heads, necks, arms and hands.