Engle had been in declining health for years from smoking-related ailments, said his attorney Stanley Rosenblatt.
Engle made U.S. legal history in 2000 when a Miami jury awarded $145 billion in punitive damages against tobacco companies in Engle's class-action lawsuit.
The Florida Supreme Court overturned that verdict as excessive, ruling that thousands of smokers covered by the Engle case must prove damages individually. Those cases are currently being tried across Florida.
Engle had a thriving pediatric practice for decades in Miami Beach. He joined the class-action lawsuit at the request of Rosenblatt, a malpractice and personal injury lawyer, and his wife, Susan, an appellate lawyer. Engle was the pediatrician for the Rosenblatts' children.
He tried to quit smoking "well over 100 times," he told the Miami Herald in 1996, which made him the ideal candidate for the class-action suit, Susan Rosenblatt said.
Engle was "a brilliant man who spent his entire life helping people and healing people and, in the process, doing a number on himself," she told the Miami Herald.
Howard Aaron Engle was born Sept. 11, 1919, in Pewaukee, Wis. He earned his bachelor's and medical degrees at the University of Wisconsin.
He said he began smoking as a student to mask the smell of the cadavers in the anatomy lab. He never paid for the tobacco, he told the Miami Herald in 2006, because representatives of "R.J. Reynolds and Chesterfield stood on street corners passing out these little five-cigarette packs."
After serving two years in the Army assigned to the public health sector in post-World War II Germany, Engle returned to the U.S. and opened his practice in Miami Beach.
He is survived by his wife, Brooke; and three children.