A panda given to Taiwan by China as a gift 14 years ago died on Saturday.
"Our medical team has confirmed that Tuan Tuan's heart has stopped," the Taipei Zoo said in a brief statement.
Previously, the panda had apparently been shaken by convulsions several times.
Tuan Tuan was 18 years old.
Tuan Tuan was reportedly drugged to do a computed tomography.
The medical team then decided to let the panda "keep sleeping" as the results indicated that his condition was unlikely to improve.
"It would have been very painful and risky for Tuan Tuan to wake him up from anesthesia," said zoo spokesman Eric Tsao.
Vets noticed Tuan Tuan was ill in August.
After initial investigations, the zoo suspected a brain tumor.
Tuan Tuan and his partner Yuan Yuan were handed over to Taiwan by Beijing in 2008, when relations between the two countries were much friendlier than they are now.
Their names combine to mean "reunion" or "unity".
The two pandas became huge stars in Taiwan and gave birth twice.
China has been pursuing its “panda diplomacy” since the end of the Cold War: the country does not sell the animals, but instead lends them to other countries for a fee.
An exception was made for Taiwan, however, as part of a Chinese charm offensive against Taiwan in the late 2000s: Tuan Tuan and Yuan Yuan were a gift.
But relations between the countries have been on hold since 2016.
Beijing has stopped all official communication.
Military threats against Taiwan have repeatedly been made in recent months.
China sees Taiwan as a breakaway territory that it wants to reunite with the mainland - if necessary using military force.