The 60-year-old man was driven out of the hospital by two carabinieri to a black minivan, and then taken away by several police cars, as images released by the police show.
From Palermo, capital of the Sicily region, Italian Prime Minister Giorgia Meloni called Denaro's arrest a "great victory for the State," while congratulating those who took part in the police operation.
The most wanted mafia boss, nicknamed "Diabolik" and "U Siccu" ("The Skinny One"), had been sentenced in absentia to life imprisonment for his involvement in the 1992 murders of anti-mafia prosecutors Giovanni Falcone and Paolo Borsellino.
Una grande vittoria dello Stato che dimostra di non arrendersi di fronte alla mafia. All'indomani dell'anniversario dell'arresto di Totò Riina, un altro capo della criminalità organizzata, Matteo Messina Denaro, viene assicurato alla giustizia. pic.twitter.com/8d6sHaDloK
A great victory for the state which demonstrates that it does not give up in the face of the mafia. In the aftermath of the anniversary of the arrest of Totò Riina, another head of organized crime, Matteo Messina Denaro, is brought to justice.
Denaro is also accused of being behind deadly bombings in Florence, Rome and Milan in 1993 that claimed ten lives. He is charged with more than 50 murders, as well as mafia association, bombings, robberies and possession of explosives, among others.
He is credited with a role in the 1993 kidnapping and subsequent murder of a 12-year-old boy, Giuseppe Di Matteo. In an attempt to dissuade his father from testifying against the mafia, Di Matteo was held captive for two years, then strangled, and his body dissolved in acid.
Maria Falcone, sister of the judge assassinated in 1992, said of the police operation that arrested Denaro: "It shows that the Mafiosi, despite their delusions of omnipotence, are ultimately doomed to defeat in conflict with the democratic state."