Taking the bus is the cheapest way to travel from Pisa to Rome. Buses traveling from Pisa to Rome depart from Pisa's Autostazione Via Pietrasantina and take just over 5 hours to arrive at Rome's Tiburtina bus station. Between 2-5 buses travel from Pisa to Rome to Pisa per day. Bus companies that travel from Pisa to Rome include Baltour and Flixbus. Ridesharing services like BlaBlaCar also frequently offer trips from Pisa to Rome. Rideshares often travel from Pisa to Rome more frequently than buses.

Taking the train is the fastest way to travel from Pisa to Rome. Trains traveling from Pisa to Rome depart from Pisa Centrale train station and take as little as 2 hours to arrive at either Rome's Termini, Tiburtina, or Ostiense train station when traveling on a high-speed train. Over 50 trains travel from Pisa to Rome every day, with the earliest train departing Pisa at 1:41 a.m. All trains that travel from Pisa to Rome are operated by Trenitalia with a variety of train types available. Some trains traveling from Pisa to Rome require a transfer in Florence.

Taking the train is the most popular way to travel from Pisa to Rome. Traveling from Pisa to Rome by high-speed train is approximately 3 hours faster than taking the bus. Trains are also only €18 more expensive than buses on average. Rome and Pisa are located too close together to make flying a prudent option. Buses remain an attractive option for people who would prefer to save while traveling from Pisa to Rome. Rideshares offer another alternative that are usually both cheaper and faster than buses.