OBJECTIVE: To compare the clinical efficacy and side effects of oral misoprostol with vaginal misoprostol for second-trimester pregnancy termination.METHODS: A randomized clinical trial of medical pregnancy termination between 14 and 26 weeks' gestation was conducted. Three misoprostol regimens were compared: 400 jig vaginally at 6-hour intervals (group 1), 400 mug orally at 3-hour intervals (group 2), and a loading dose of 600 mug vaginally followed by 200 mug orally at 3-hour intervals (group 3). A sample size of 225 women was required for equivalence of the three regimens, with an interim safety analysis planned at 80 women.RESULTS: A significant difference between the groups was evident at the interim safety analysis and the study ceased. The subset of 84 women recruited before the study closure is described. There was a significant difference in the median time to achieve delivery among the three groups: group 1, 14.5 hours (95% confidence interval 12.0, 16.9), versus group 2, 25.5 hours (13.5, 23.8), versus group 3, 16.4 hours (interquartile range 14.2-37.3) (P = .042). Within 24 hours of commencement 85.7% of women in group 1, 44.8% in group 2, and 74.1% in group 3 delivered (P = .003). At 48 hours 0% in group 1, 20.7% in group 2, and 3.7% in group 3 were undelivered (P = .011). There was no difference in women's perceptions of the termination process.CONCLUSION: In second-trimester pregnancy termination, a vaginal misoprostol regimen of 400 jig every 6 hours was 1.9 times more likely to result in delivery within 24 hours from commencement than an oral regimen of 400 mug every 3 hours. (C) 2003 by The American College of Obstetricians and Gynecologists.