Staff in Ireland, Germany, Sweden, Belgium and the Netherlands agreed to stage a 24-hour walkout forcing the cancellation of 396 flights.
Although Spanish pilots did not join the strike, the industrial action affected 78 flights to and from Spanish airports.
That means some 14,000 could face cancellations during Friday.
Routes affected are those between the Dutch airport of Eindhoven to Reus and Valencia and 54 flights between Germany and Spain, 20 to and from destinations in Belgium. Four flights between Stockholm and Alicante or Barcelona have also been cancelled.
Ryanair promised the minimum distruption:
The strikes follow walkouts by Ryanair staff on July 25th and 26th which brought travel chaos during two of the busiest days of the summer holiday