Angel Diaz, 55, proclaimed his innocence at 6 p.m. Wednesday before he was given the first intravenous sedative at the Florida State Prison.
In what took three times as long as most executions, Diaz grimaced, flexed his jaw as if in pain and a hooded doctor administered a second dose of the drug to stop the heartbeat, the Miami Herald reported.
He was pronounced dead at 6:34 p.m.
State prisons spokeswoman Gretl Plessinger said Diaz did not suffer any pain, and that the second dose was required because he had liver disease, which slowed his metabolism.
Diaz was condemned to death for the 1979 shooting death of a strip club manager in Miami during a robbery by three men. Diaz had also been sentenced to life in prison in Puerto Rico for another killed but escaped to the United States.
He was the fourth person Florida executed this year.