In addition to the 4.3 tonnes of cocaine, investigators also seized €1,850,000 in cash, making it one of the largest raids of its kind in Europe.
The Italian investigation focused on cocaine distribution between the Otoniel’s Clan del Golfo gang and mafia groups from Veneto, Lombardy, Lazio and Calabria.
Police posed as undercover transport operators to seize 19 controlled deliveries of cocaine in the country between May 2021 and May 2022.
It was part of a year-long operation involving both the Colombian judiciary and US Homeland Security targeting the Clan del Golfo cartel, who operate in 28 countries around the world.
The international investigation resulted in arrest warrants being issued for 38 people in six countries including Italy, Colombia, Slovenia, Croatia, Bulgaria, and the Netherlands.
It comes after Colombia extradited Otoniel, who had been the country's most wanted drug lord before his capture, to the United States last month, where he faces indictments in three federal courts.
Otoniel was arrested after a seven-year hunt by Colombian special forces who moved in on his jungle hideout in October with 500 soldiers and 22 helicopters.
Prior to his capture, Colombia's government had offered a $800,000 (€734,000) reward for information about his whereabouts, while the US placed a $5m bounty on his head.
His arrest has been hailed the greatest takedown of a dangerous drug trafficker since that of Pablo Escobar in 1993.
Otoniel was the alleged head of the Gulf Clan, which is believed to consist of approximately 1,800 armed members. Members have been arrested in Argentina, Brazil, Honduras, Peru and Spain.
The European cocaine super cartel is made up of the Irish Kinahan mafia, the Balkans' Tito and Dino cartel, the Dutch Mocro Mafia and the Italian Camorra and had close links with the Colombian drug kingpin.
An investigation by the Sunday World based on EU drug reports, source information and reports published across the Balkan territories found that the Kinahan organisation can be directly linked to Otoniel.
It is believed that hundreds of tonnes of cocaine were ordered directly for the European market through the relationship and during meetings deep in the Colombian jungles.
Sources say that Daniel Kinahan was the mastermind behind merging the European and Colombian groups, with each cartel bringing money and contacts together.
"Each had something unique to bring, whether they could offer a money laundering service, control of the major entry points into Europe at Antwerp or Rotterdam or the connections with the Colombian bosses who control the 600,000 acres of cocaine production land,” a source said.
"It has been an extraordinary time for Europe. Each member of the big four European groups had something vital to offer the other. The merging of these groups has resulted in this tsunami of cocaine we describe that has hit Europe."