Supported by a coordination centre at Eurojust, judicial and law enforcement authorities from the Netherlands, Italy, Germany and Belgium executed the arrests and seizures against 'Ndrangheta, an organized crime group based in Calabria, Italy, for cocaine trafficking, money laundering, bribery and violence.
In Germany, federal police said there had been multiple arrests in the early morning raids.
In Germany, the operation focused on restaurants, offices and apartments, mainly in the states of North Rhine-Westphalia and Bavaria, with 21 suspects targeted.
"This shows that worldwide crime can be tackled well if we work well together", said Eurojust Vice-President Filippo Spiezia.
He said over 3,000 kilogrammes of cocaine was seized in the Netherlands along with 140 kilogrammes of ecstasy pills and 2 million Euros in cash.
Officials hailed Wednesday's operation as a serious blow to the group.
"Obviously we have not defeated 'Ndrangheta with this operation - 'Ndrangheta is extremely powerful and extremely rich", he said.
Here are all the 5G devices coming in 2019... so far
Qualcomm has announced Snapdragon 855 , the upcoming flagship SoC that will be found in most of the flagship devices in 2019. While the physical device was missing in action at the summit, Samsung did show off a prototype device with quite the notch .
The European police agency Europol said it was a "decisive hit against one of the most powerful Italian criminal networks in the world".
Italian anti-mafia prosecutor Federico Cafiero De Raho said the operations would affect the 'Ndrangheta's drug trafficking operations around the world, including Colombia, Ecuador and Brazil.
The investigation also involved operations in the South American country of Suriname. His arrest was among the 46 people taken into custody.
It is the only mafia organisation operating on all continents, say prosecutors, and is believed to now be the most influential Italian organised-crime group.
European Parliament President Antonio Tajani, who is Italian, sent "congratulations" to the police forces involved, adding: "Europe fights 'Ndrangheta criminal groups".
Dutch outlet NOS said that the 'Ndrangheta is known to operate its drug smuggling through the country's vibrant flower-trading industry.
The raids came a day after Italian police arrested Settimo Mineo, the new head of Sicily's Cosa Nostra mafia.
Just under half of the suspects were detained in Italy.