BACKGROUND: The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety. The absolute and relative risks associated with a trial of labor in women with a history of cesarean delivery, as compared with elective repeated cesarean delivery without labor, are uncertain. METHODS: We conducted a prospective four-year observational study of all women with a singleton gestation and a prior cesarean delivery at 19 academic medical centers. Maternal and perinatal outcomes were compared between women who underwent a trial of labor and women who had an elective repeated cesarean delivery without labor. RESULTS: Vaginal delivery was attempted by 17,898 women, and 15,801 women underwent elective repeated cesarean delivery without labor. Symptomatic uterine rupture occurred in 124 women who underwent a trial of labor (0.7 percent). Hypoxic-ischemic encephalopathy occurred in no infants whose mothers underwent elective repeated cesarean delivery and in 12 infants born at term whose mothers underwent a trial of labor (P<0.001). Seven of these cases of hypoxic-ischemic encephalopathy followed uterine rupture (absolute risk, 0.46 per 1000 women at term undergoing a trial of labor), including two neonatal deaths. The rate of endometritis was higher in women undergoing a trial of labor than in women undergoing repeated elective cesarean delivery (2.9 percent vs. 1.8 percent), as was the rate of blood transfusion (1.7 percent vs. 1.0 percent). The frequency of hysterectomy and of maternal death did not differ significantly between groups (0.2 percent vs. 0.3 percent, and 0.02 percent vs. 0.04 percent, respectively). CONCLUSIONS: A trial of labor after prior cesarean delivery is associated with a greater perinatal risk than is elective repeated cesarean delivery without labor, although absolute risks are low. This information is relevant for counseling women about their choices after a cesarean section. Copyright © 2004 Massachusetts Medical Society.