Riina, who had been serving 26 life sentences and is thought to have ordered more than 150 murders, had been in a medically induced coma after his health deteriorated following two operations.
The mobster, who turned 87 on Thursday, died in the prisoners' wing of a hospital in Parma in northern Italy, the government said.
Nicknamed "The Beast" because of his cruelty, Salvatore "Toto" Riina led a reign of terror for decades after taking control of Sicily's powerful organised crime group Cosa Nostra in the 1970s.
The highest-profile murders he ordered were those in 1992 of anti-mafia judges Giovanni Falcone and Paolo Borsellino, who had worked to bring more than 300 mobsters to trial in 1987.
"Riina will go down in history as the man who destroyed Cosa Nostra," Mafia expert Attilio Bolzoni said.
"With his strategy of bloody massacres in Sicily and across Italy... he turned an invisible Mafia visible, with hundreds, thousands of murders, carried out first with Kalashnikovs, then bombs."
- 'No mercy' -
But other anti-mafia experts warned that the demise of the ex-superboss did not mean the end of Cosa Nostra.
"We must not lower our guard," Interior Minister Andrea Orlando said.
"Though it may be less noisy and bloody today, it is no less dangerous. The Mafia knows how to adapt," he said.
As anti-mafia prosecutor Giovanni Russo wryly noted, "business without gunshots is better business, so violence has become the last resort" for the criminal group, which harbours ambitions for "international expansion".
Riina's family had been given permission Thursday by Italy's health ministry for a rare visit to say goodbye, though Italian media reported that neither his wife nor children had made it in time.
"You're not Toto Riina to me, you're just my dad. And I wish you happy birthday dad on this sad but important day, I love you," one of his sons, Salvatore, wrote on Facebook.
Among his most famous crimes, Riina ordered the brutal murder of a 13-year-old boy who was kidnapped in a bid to stop his father from spilling Mafia secrets. The boy was strangled and his body dissolved in acid.
"God have mercy on him, as we won't," an association for victims said of Riina in comments to the Fatto Quotidiano newspaper.
The Italian bishops conference ruled out a public church funeral for Riina.
"I'm not happy about his death, but I cannot forgive him," said Maria Falcone, sister of the anti-mafia judge Giovanni Falcone murder on Riina's orders.
"According to my religion, I could have forgiven him had he ever repented, but no sign of redemption ever came."
- 'No regrets' -
The ageing gangster was caught on a wiretap this year saying he "regrets nothing... They'll never break me, even if they give me 3,000 years" in jail.
The son of a poor farmer, he was born on November 16, 1930, in Corleone, a village near Palermo that would become synonymous with the Mafia through Francis Ford Coppola's popular "Godfather" film trilogy.
He lost his father and a brother while still young when they were blown up trying to extract gunpowder from an unexploded American bomb in 1943. By the time he was 19, he had killed his first victim.
He started off as a foot soldier to boss Luciano Leggio before moving up the ranks, going on the run in 1969 but continuing to lead first the Corleone clan and then the entire Sicilian mob while in hiding.
He would elude police efforts to snare him for almost a quarter of a century, without ever leaving Sicily.
Riina was sentenced to several life sentences in absentia after a fellow mobster turned state witness.
The "Beast" retaliated by ordering the deaths of 11 of the turncoat's relatives. He was eventually captured in 1993 after a tip-off from a rival.
"Riina was still powerful even from prison. He gave his orders and what could be done was done," Gaspare Mutolo, a turncoat who shared a cell with the boss, told journalists in Rome on Friday.
Pietro Grasso, Italy's senate speaker and a former anti-mafia magistrate, was among many to lament the fact that Riina took multiple secrets with him to the grave.
The mobster's eldest daughter Maria Concetta mourned by posting a picture on Facebook of a finger pressed to the lips and the word "shhh...", a likely reference to the Mafia code of 'omerta' -- a vow of silence.
Source:AFP
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