The Tremiti Islands are accessible only by sea. Regular ferry and hydrofoil services operate year-round from Termoli on the Molise coast, with the crossing taking about 1–2 hours depending on the type of vessel. Termoli is itself easily reached by train from Rome (3.5 hours) or Bari (2 hours).
Seasonal services from late spring through early September also operate from Vasto, Pescara, Rodi Garganico, and other Adriatic ports. These are generally slower and less frequent than the Termoli connection but can be useful depending on where you are coming from. Hydrofoil services (aliscafo) are faster but more expensive than the regular ferry, and may not run in rough sea conditions.
There are no cars on San Domino or San Nicola — the islands are small enough to explore entirely on foot, which is part of their appeal.