Objective: This study was undertaken to compare the efficacy and side effects of a high-dose vaginal misoprostol regimen to concentrated intravenous oxytocin plus low-dose vaginal misoprostol for midtrimester labor induction. Study design: Women at 14 to 24 weeks, with obstetric or fetal indications for delivery and no prior cesarean, were randomly assigned to receive either vaginal misoprostol 600 μg × 1, then 400 μg every 4 hours × 5 (group 1) or escalating dose-concentrated oxytocin infusions (277-1667 mU/min) plus vaginal misoprostol 400 μg × 1, then 200 μg every 6 hours × 2, then 100 μg × 1 (group 2). Analysis was by intent to treat. Primary outcomes were live birth rate and induction-to-delivery interval. Results: The intended sample size was 70 women per group; however, the trial was terminated at the initial interim analysis because of a highly significant difference in 1 of the primary study outcomes. Twenty women were assigned to group 1 and 18 were assigned to group 2. Median induction-to-delivery interval was significantly shorter in group 1 (12 hours, range 4-44 hours) versus group 2 (18 hours, range 7-36 hours; P = .01). Induction success rate at 12 hours was significantly higher in group 1 (60%) compared with group 2 (22%, P = .02). No significant difference was noted in the live birth rate between groups 1 and 2 (13%, 0%, P = .16). The incidence of retained placenta requiring curettage, chorioamnionitis, intrapartum fever, nausea, emesis, and diarrhea were similar between both groups. Conclusion: Compared with concentrated oxytocin plus low-dose vaginal misoprostol, high-dose vaginal misoprostol significantly shortens midtrimester labor inductions. © 2005 Mosby, Inc. All rights reserved.