Mark James Asay (53) had been on death row since 1988 for shooting dead two men
Florida has put a man to death with an anaesthetic never used before in a US lethal injection.
Mark James Asay, 53, is the first white inmate to be executed in the state for killing a black man since the 1970s, the Death Penalty Information Centre said.
He was pronounced dead at 6.22pm local time on Thursday at the state prison in Starke.
Asay received a three-drug injection that began with the anaesthetic etomidate, criticised by some as being unproven in an execution.
It replaced midazolam, which became harder to acquire after many drug companies began refusing to provide it for executions.
Asked whether he wanted to make a final statement before his execution, Asay said: "No sir, I do not. Thank you."
Michelle Glady, a spokeswoman for the corrections department, said there was no complication in the procedure and that Asay did not speak during it.
Asay had been on death row since 1988 for shooting dead two men in Jacksonville.
The landmark decision to execute him was made by Florida's Supreme Court, which effectively outlawed capital punishment for 15 years from 1964.
But while 90 men and two women have been executed since it was ruled lawful again, the latest case has become a historic one.
One state Supreme Court judge said Asay was the "proverbial guinea pig".
Justice Barbara Pariente said the drug used to kill him had violated a key constitutional protection against cruel or unusual punishment.
She voted to halt the execution but was defeated by a majority of colleagues who allowed it to go ahead.
Asay's legal team said the chemical causes pain before it takes hold.
They added it causes involuntary body movements that make it difficult for prison staff to know "when the guy is conscious".