Objective: To evaluate the efficacy of high-dose oral misoprostol for mid-trimester pregnancy interruption. Methods: We reviewed our experience with high-dose oral misoprostol for mid-trimester pregnancy interruption from November 1995 to May 1999. Patients undergoing labor induction for intrauterine fetal demise or medically indicated pregnancy termination at 13–32 weeks of gestation with a non-dilated cervix were evaluated. Patients received 400 µg misoprostol orally every 4 h. Women undelivered within 24 h were considered failures and were treated with high-dose oxytocin as previously described. For comparison, a group of women treated with high-dose oxytocin were evaluated. Results: Forty-seven pregnancies were managed with misoprostol (n = 23) or high-dose oxytocin regimen (n = 24). Both groups were similar with respect to induction indication, gestational age, maternal age/parity, laminaria use, and initial cervical dilation. Induction-to-delivery interval (mean ± SD) was significantly shorter in the misoprostol cohort (15.2 ± 6.7 h) compared with those treated with oxytocin (21.7 ± 11.0 h; p = 0.02). Additionally, a significantly greater percentage of women treated with misoprostol delivered within 24 h (91.0%) compared with the oxytocin group (62.0%; p = 0.04). Adverse outcomes and side effects were not significantly different between the study groups. Conclusion: High-dose oral misoprostol is more effective than concentrated oxytocin infusion for mid-trimester pregnancy interruption.