OBJECTIVE: To compare the effectiveness and side effects of oral and vaginal misoprostol for the termination of second and third trimester pregnancy with intrauterine fetal death.METHODS: Eighty pregnant women at 16–41 weeks’ gestation with intrauterine fetal death were randomized in two groups to receive either 400 µg of misoprostol orally every4 hours (n=40) or 200µg of misoprostol vaginally every 12 hours (n = 40) until the termination of pregnancy was completed. The adverse effects, progress, and outcomes of delivery were assessed.RESULTS: The groups were similar in age, weight, height, gestational age, parity, and modified Bishop scores before intervention. The mean induction-to-delivery time in the oral group (13.95 [standard deviation (SD) = 5.63] hours) was significantly shorter than the time in the vaginal group (18.87 [SD = 10.38] hours, P = .001). The number ofdeliveries within 24 hours after the initial drug administration in the oral group (92.5%) was significantly higher than the number in the vaginal group (67.5%, P < .001), and all delivered within 48 hours after the initial drug administration. However, the gastrointestinal side effects in the oral group was significantly higher than in the vaginal group (P= .005).CONCLUSION: Misoprostol (400 µg given orally every 4 hours) was more effective than misoprostol (200 µg given vaginally every 12 hours) for the termination of second and third trimester pregnancy with intrauterine fetal death, but with more gastrointestinal side effects.