You can fly to San Juan Puerto Rico SJU airport, or to Aguadilla BQN airport.

Most companies fly to SJU which is far from Mayaguez (164Km, about 2.5 hours driving).

BQN is served only by domestic US flights, including low cost companies like Jet Blue and Spirit. Aguadilla is about 37 Km from Mayaguez, 45 min driving. If you have connections to BQN, you are advised to fly there.

JET BLUE flies to BQN from JFK

SPIRIT flies to BQN from Fort Lauderdale and Orlando

CONTINENTAL flies to BQN from Newark EWR.