Roy Black, a nationally prominent defense lawyer who successfully defended William Kennedy Smith in his 1991 trial for rape and helped Jeffrey Epstein secure a plea deal in 2008 that enabled him to escape federal sex-trafficking charges, died on Monday at his home in Coral Gables, Fla. He was 80.

His law partner Howard Srebnick confirmed the death without specifying the cause, saying only that Mr. Black had dealt with a “serious illness.”

Mr. Black defended the notorious and the obscure, celebrities and sports stars. His clients included Justin Bieber and Rush Limbaugh, as well as Florida police officers accused of misconduct. He usually emerged victorious from his courtroom battles.

But it was the acquittal he won for Mr. Smith — a 30-year-old nephew of President John F. Kennedy and Senators Robert F. and Edward M. Kennedy — that gave Mr. Black a national profile, in a case that tested the outer limits of power and influence.

The trial pitted the word of an accuser — later identified in the news media, including by The New York Times, as Patricia Bowman, whom Mr. Smith had met at a local bar — against the word of a member of one of America’s most powerful families.

Mr. Black made full use of the disjunction between accuser and accused, eliciting emotional testimony from Senator Edward Kennedy and from his nephew.