Víazul (tel. 7/881-1143 in Havana; www.viazul.com) has daily buses to Sancti Spíritus on the Havana-Santiago de Cuba line leaving at 9:30am, 3pm, 6:15pm, and 10pm. From Havana, the trip takes just over 5 hours. The fare is CUC$23. Víazul also makes the 1-hour trip to Sancti Spíritus directly from Trinidad (tel. 41/99-4448; CUC$6) daily at 8am on the Trinidad-Santiago de Cuba route. From Santiago, buses leave at 9am, 3:15pm, 7:30pm, and 10pm, and the trip takes around 10 hours. The fare is CUC$28.
The bus terminal in Sancti Spíritus (tel. 41/32-4142) is located at Carretera Central Km 388, between Circunvalación and the Carretera de Jíbaro. Taxis charge CUC$2 or CUC$3 for a ride to the center of town.
Driving from Havana, the fastest route is along the Autopista Nacional (A1) to Santa Clara, and then continuing along the Carretera Central to Sancti Spíritus (about 5 hr.). The short drive from Trinidad, along the Circuito Sur, is one of the prettiest in Cuba, as the road rolls through fields of sugar cane with the Sierra del Escambray looming in the background. From Santiago de Cuba, start out northwest on the unfinished A1 and then take the Carretera Central through Bayamo, Camagüey, and Ciego de Avila (about 6 hr.).