US officials said more than $60m in cash had been seized
Police in four nations have held about 200 people over alleged trans-Atlantic drug trafficking involving a major Mexican drugs cartel.
US and Italian police seized 175, some of them picked up in Italy's Reggio Calabria region, where the N'drangheta mafia run the cocaine trade.
Other suspects were arrested in Mexico and Guatemala.
US Attorney General Michael Mukasey said the arrests came after a 15-month investigation into the Gulf cartel.
The cartel is already believed to have links to organised crime in Italy.
It is suspected of importing and distributing tonnes of drugs from Latin America into the US.
The US Drug Enforcement Administration said three alleged cartel leaders had been indicted.
Italian police say the coordinated investigation, Operation Solare, has proved to be one of its biggest operations against the mafia in recent years, and one of their most successful.
The N'drangheta is notoriously secretive and ruthless, characteristics which have protected its drug-trafficking hegemony until now, the BBC's Emma Wallis reports from Rome.
The US and Italian charges cover various crimes, including trafficking of cocaine and marijuana, kidnap charges, attempted murder, conspiracy to use a firearm in a violent crime and conspiracy to kill and kidnap in a foreign country.
Mr Mukasey said it was a "massive assault" on the drug cartel, and praised the international co-operation.
The suspects detained in the US were arrested in a dozen states, including 43 people picked up in Atlanta, Georgia.
Nicola Gratteri, the Italian public prosecutor for the anti-mafia district attorney's office of Reggio Calabria, said: "This operation exemplifies the European vision of the international fight against drug-trafficking."
More than 16,000kg (35,000lb) of cocaine, 450kg of methamphetamine, 9kg of heroin, 23,300kg of marijuana, 176 vehicles and 167 weapons have been seized.
Approximately $60.1m (£33m) in US currency was also taken.