To evaluate the maternal and fetal outcomes of a large cohort of women treated with prostaglandin E2 (PGE2) gel for cervical ripening prior to trial of labor after previous cesarean delivery. Beginning in 1990 all pregnant patients with previous cesarean delivery presenting for prenatal care at 10 California hospitals were prospectively studied. We analyzed multiple parameters to compare outcomes of cases in which PGE2 gel was used to outcomes in a control group in which PGE2 was not used. Data were examined by X2 testing. During the study period 5022 patients underwent trial of labor after prior cesarean delivery. Of these 5022 patients, 453 (9%) were treated with PGE2 gel. There was no significant difference in the incidence of uterine rupture between the PGE2 group and the control group. Indicators of maternal and perinatal morbidity were not significantly higher in the prostaglandin treated group. The use of PGE2 gel for cervical ripening appears to be relatively safe in patients with prior cesarean delivery.