The airline, which says its pilots have some of the best conditions in the low-priced sector, said it planned to cancel 30 of 290 flights from Ireland on Thursday.
Pilots in Ryanair's home country Ireland held a strike for the first time on Thursday as they demanded better conditions from Europe's largest low-priced carrier, which is trying to stave off a wave of industrial action across Europe.
The airline - who recently revealed they will charge passengers more for baggage - have had to cancel 30 of their flights leaving today.
Forsa had said late Wednesday that talks with Ryanair had ended after seven hours of talks with "very little progress".
Why are pilots on strike?
It read: "Ryanair pilot union talks conclude without agreement".
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But they have reassured passengers that all Ireland to Europe flights will operate as normal.
Customers were informed via text and email of the cancellations, with Ryanair offering a refund to those affected.
The pilots' union Fórsa, of which the Irish Airline Pilots' Association (IALPA) is a branch, had earlier said it was not optimistic that a deal could be reached to avert the strike.
On Twitter, Ryanair said: "We respect but regret the decision of 25% of our Irish pilots to go on strike, but believe that they should take up our offer of working groups so we can resolve these issues".
"We will do this by cancelling a number of flights on high-frequency routes from Ireland to London and other United Kingdom province destinations where customers can transfer readily to other flights on Thurs or switch their travel to Friday, Saturday or subsequent days".
"Ryanair pilots have already secured a 20% pay increase, earn up to €200,000 p.a., work 5 days-on, followed by 4 days-off (a double bank holiday weekend at the end of every week), enjoy rapid promotions and unmatched job security".