The arrests in Italy, Germany, the Netherlands and Belgium came as part of an investigation code-named Pollino that was launched in 2016 against the 'ndrangheta criminal group on allegations of cocaine trafficking, money laundering, bribery and violence, said Eurojust, the European agency that fights cross-border organized crime, which coordinated the operation.
Police swooped on locations in Italy, Germany, the Netherlands and Belgium in a series of co-ordinated raids.
The 'Ndrangheta, a mafia organisation that operates out of the Calabria region of southern Italy, is one of the largest crime syndicates in the world, and is thought to make billions of pounds through cocaine trafficking every year.
He said that fighting organized crime across state lines "requires judicial instruments like the ones used in this occasion in Europe, which allowed us to coordinate our regulations, and enabled us to counter 'Ndrangheta".
Report says the group runs its global operations from a base in southern Italy.
"This shows that global crime can be tackled well if we work well together", said Eurojust Vice-President Filippo Spiezia.
Law enforcement and judicial officials speak at a press conference organized by Eurojust in The Hague, Netherlands, on December 5, 2018. On Tuesday, Italian authorities said they had dismantled the rebuilt upper echelons of the Mafia in the Sicilian capital of Palermo by arresting 46 people, including the man presumed to have taken over as provincial kingpin.
Some 140 kilograms of ecstasy pills and 3 000-4 000 kilos of cocaine were seized during the operation, Dutch prosecutor Fred Westerbeke said at a press conference in The Hague on Wednesday.
The "Ndrangheta is seen as the most powerful Italian mafia organization, trumping Sicily's Cosa Nostra and Naples" Camorra.
"They are invisible", Cafiero de Raho added.
Among the 'ndrangheta clans hardest hit by Wednesday's raids was the Pelle-Vottari crime family, investigators said.
Some 2 million euros (2.3 million dollars) in criminal assets was seized, Eurojust Vice-President Filippo Spiezia said in The Hague.
Italian police said 90 people had been arrested so far in the operation targeting the 'Ndrangheta group and its "projections across South America".
But some express caution and said the mafia will continue to pose threat as the group still has resources and is operating across the world.
Eurojust said those arrested Wednesday included "high-ranking members of the Mafia network", but didn't release their names.