Mohammed Nasif Khayrbik, a senior Syrian government security official close to President Bashar al-Assad, died on Sunday morning after a long illness, state media said.
Khayrbik was a key confidante of the Assad family and the target of EU and US sanctions for his alleged role in putting down anti-government demonstrations and interfering in neighbouring Lebanon.
"The presidency announces the death this morning of retired general Mohammed Nasif Khayrbik, deputy vice-president of the republic, after a long illness," Syrian state television said.
Khayrbik's ties to Syria's ruling family go back to the days of Hafez al-Assad, Bashar's father and predecessor as president.
Khayrbik was an advisor to him, and oversaw ties with Iran, and well as US-Syrian relations.
He remained close to the presidential palace after Bashar al-Assad succeeded his father, and in the 1990s served as chief of the country's internal security.
In 2005, he was named vice-president for security affairs.
In 2007, he was targeted by US sanctions for allegedly aiding efforts by Damascus "to undermine Lebanese democracy."
And in May 2011, after security forces moved to put down protests against Assad's regime, Khayrbik was among the officials added to an EU travel ban and asset freeze list.