Objectives: Using surgical methods compared to medical methods, such as misoprostol for termination of pregnancy, has several side effects. This study was performed in order to compare the effect of vaginal and oral misoprostol in second-trimester pregnancy termination (14 - 24 weeks). Materials and Methods: The authors performed a clinical trial study in 40 pregnant women at 14 to 24 weeks of gestation and candidates for medical interruption of pregnancy. All patients received 600 μg of vaginal misoprostol as primary dosage and then, were placed randomly in two groups consisting of 20 patients that received 400 μg of vaginal or oral misoprostol, every four hours, up to three doses. If the abortion was incomplete, oxytocin was used. Twenty-four hours after the procedure, uterine sonography was performed in all patients and if residue was found, the patients were then candidates for curettage. Results: Seventeen patients (85%) in the vaginal group and 17 patients (85%) in the oral group had successful pregnancy interruption. The mean interval until the discharge of pregnancy products in the vaginal group (15 / 42 ± 10 / 84) showed no significant difference compared to the oral group (12 / 65 ± 7 / 8) and no significant differences in side-effects were found between the two groups. Conclusion: Oral misoprostol is as effective as vaginal misoprostol in performing second-trimester abortion. It appears that the vaginal misoprostol primary dose together with the continuation of oral dose is not more effective compared to the vaginal misoprostol method alone.