RFA Argus, Royal Marines and US Coast Guard teams collaborated with Dutch Navy ship HNLMS Groningen which led to them seizing 1.7 tonnes of cocaine and 28kg of amphetamines.
It was the second drug bust in two days, as they seized 264kg of cocaine in a separate operation just 48 hours earlier.
Minister for the Armed Forces James Heappey said: "The Royal Navy has once again demonstrated its professionalism and tactical operational capability in an international effort to stop illegal drug-smuggling.
"It is with thanks to their efforts that £160 million worth of drugs will never reach the streets of the UK."
The most recent bust came as RFA Argus was conducting routine training, one of the Merlin helicopters spotted a suspicious craft.
The Royal Fleet Auxiliary vessel changed course to give chase and the Merlin and Wildcat helicopters worked with HNLMS Groningen to allow the US Coast Guard to intercept the craft.
Commanding Officer of RFA Argus, Captain Kevin Rimell said: "This recent interdiction is yet another example of multi-national co-operation in the Caribbean.
"I am proud that the team of RFA Argus, utilising 815 and 845 Naval Air Squadron helicopters, boats crewed by RFA personnel and Royal Marines from 47 Commando, were able to take the lead in an operation alongside our US Coastguard and Dutch Navy colleagues.
"Collectively we secured and apprehended a number of smugglers and a large quantity of contraband.
"These are challenging times and we ask a lot of our people so it is encouraging to see that our training and professionalism continues to shine through."
After three separate drug busts that took place last month, the Royal Navy Caribbean task group has now prevented nearly £250bn worth of drugs from being sold.
In September, a Royal Navy task group has landed a triple blow to drugs traffickers in the Caribbean after seizing cocaine that would be worth an estimated £81m on Britain's streets.
Sailors, Royal Marines and the US Coast Guard team on board support ship RFA Argus hauled 11 bales of cocaine weighing 358 kilogrammes in the first of three busts in seven days.
Patrol ship HMS Medway and her US Coast Guard team followed that up by catching traffickers in two interceptions inside 24 hours in the Caribbean Sea, which saw 650 kilogrammes of cocaine seized, never to reach the streets.
Commanding Officer of HMS Medway, Lieutenant Commander Jim Blythe, said: "The Royal Navy and the US Coast Guard have prevented a significant quantity of drugs crossing the Caribbean that could have been destined for the streets of the UK."
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