The National Crime Agency and PSNI are investigating a crime group suspected of trying to import cocaine worth £1m.
Three men have been arrested in the Essex area and two in the north of Wales – four of them are known to be based in Northern Ireland, while one is from the north of England.
The men, who were detained on Thursday and have since been released on bail, are all aged between 21 and 59.
Three lorries were seized as part of the operation and around 21 kilos of cocaine was found in what officers described as a “complex concealment”.
Searches have also been carried out at a number of properties in Northern Ireland.
The investigation has also been supported by An Garda Síochána and the Organised Crime Task Force.
NCA Regional Head of Investigations Gerry McLean said: “This is a highly significant operation in terms of our activity to target organised crime impacting on Northern Ireland.
“In making these seizures, we have both prevented a large quantity of drugs from reaching our streets, and denied criminals an important avenue for smuggling.”
Detective Superintendent Rachel Shields, from the PSNI’s Criminal Investigation Branch, said: “Our detectives have been working in collaboration with the NCA in relation to this operation for some time.
“These arrests and seizure are significant in terms of the quantity seized, and in terms of the disruption caused to organised criminals.
“We will continue to work closely with and support the NCA in their work to disrupt the nefarious activities of organised crime groups.”