The Saturday surgery was to remove an obstruction in the Komodo dragon's intestine that made the reptile act lethargically and stop eating, the Pittsburgh Post-Gazette reported.
The reptile -- named Noname -- was born in 1993 and given to the zoo in 1997.
"It's certainly one of our favorite animals at the zoo. It's a shock," said Henry Kacprzyk, curator of reptiles and Kids Kingdom at the Pittsburgh Zoo & PPG Aquarium in Highland Park.
Noname was 9 feet long and weighed 230 pounds when he died, the Pittsburgh Tribune-Review reported.
Komodo dragons are known to be very aggressive and have a deadly bite as their mouths are breeding grounds for toxic bacteria.
"He was never aggressive," Kacprzyk said. "We had this animal that was as nice as any animal you could work with. He liked to be talked to and scratched [on his head]."
Komodo dragons are considered an endangered species, the zoo's Web site states, with only 5,000 remaining worldwide.
"I would hope to be able to replace this animal but getting another Komodo dragon is not like getting another Noname," Kacprzyk said.