Background: Pharmacological studies suggest that sublingual route might be the optimal route of administration for PGE1 analogue misoprostol because the avoidance of the first pass hepatic circulation would yield bioavailability like that achieved with the vaginal route along with an earlier onset of action and a prolonged activity. Objective: The aim of this study was to compare the efficacy and the safety of vaginal misoprostol with sublingual misoprostol for induction of labor in post-term pregnancy. Subjects and Methods: This study included 50 cases, each with a singleton post-term pregnancy and a live fetus requiring induction of labor were allocated to sublingual and vaginal administration of misoprostol. Outcome measures related to labor and maternal and fetal side effects were compared between the 2 groups and evaluated using Chi square test. Results: The sublingual route of misoprostol was associated with a reduced risk of failed induction, reduced time from initiation to induction, reduced induction to delivery interval and a higher incidence of maternal and fetal side effects. However, the differences were not statistically significant. Conclusion: The sublingual route of administration of misoprostol is comparable in efficacy and safety to the vaginal route for induction.