Abstract: The purpose of this study was to compare the efficacy and side effects of two different misoprostol regimens for second-trimester pregnancy termination. Sixty women in second trimester of gestation with indications for pregnancy termination were randomly assigned in two equal groups to receive either vaginal or oral misoprostol. The dosing regimen was 400 μg as the initial dose followed by 400 μg up to 3 doses (1200 μg) if needed in each group. Efficacy and side effects were compared. The percentage of women who delivered was significantly higher in vaginal group than the oral group (86.7 vs. 43.3 p = 0.0006). No significant differences in complication rates and induction to delivery interval were noted between the two groups. Vaginal administration of misoprostol resulted in a higher success rate for second trimester pregnancy termination, whereas, no significant differences in induction to delivery time and complication rates were noted between vaginal and oral groups.