The Aer Lingus service between Shannon Airport and London Heathrow comes to an end on Sunday after almost 60 years.
The company decided last August to transfer its Heathrow slots to Belfast International, where its three times a day service to London begins on Monday.
The move caused uproar in the Shannon area, where fears were voiced that the move would have disastrous consequences for jobs and tourism.
Aer Lingus insisted it was a commercial decision which would be proved right.
It is the fourth of nine new routes at Belfast International begun by the airline since it decided to set up its new UK hub there.
Strike averted
The decision also proved controversial in Belfast, where a strike by Aer Lingus cabin crew and ground staff over the new pay and conditions in Northern Ireland was averted at the last minute.
The move could spark a price war around London flights as Aer Lingus goes head to head with British Midland which operates its Heathrow route from George Best Belfast City Airport.
It will also be in competition with easyJet which flies from Belfast International to the other London airports of Stansted, Gatwick and Luton.
Flybe operates a Gatwick route from the City Airport, while Ryanair has recently begun a service from there to Stansted.
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