Aims: To evaluate the impact of induction of labor with vaginal tablets of prostaglandin E2 on the rate of cesarean section (CS), and to identify possible predictors of successful vaginal delivery. Methods: 1541 consecutive women admitted for induction of labor with vaginal tablets of PGE2 were retrospectively compared with 574 consecutive women with spontaneous onset of labor. Results: Maternal age, nulliparity, previous CS, gestational age, and birth weight were similar in the study and control groups. The CS rate was twofold higher in the study group (20.7% vs 10.6%). CS rates in the study and control groups were 26.9% and 12.8% for the nulliparous women, and 11.2% and 5.1% for the multiparous women with no previous CS. Neither group had major maternal or fetal complications. A logistic regression model and stepwise analysis showed that nulliparity, previous CS, maternal age, number of PGE2 applications, birth weight, and the induction of labor by itself were independent significant risk factors for increased CS rate. Conclusions: Induction of labor with vaginal PGE2 tablets results in a vaginal delivery rate of 79.3%, with apparently no serious maternal or fetal complications. Nulliparity, and previous CS are the most significant risk factors for increased CS rate. However, even after these risk factors are excluded and controlling for possible predictors for CS, PGE2 induction is independently associated with a twofold increase in CS rate, most often because of labor dystocia.