Objective: To estimate whether vaginal isosorbide mononitrate, added to oral misoprostol for cervical ripening and labor induction, shortens time to vaginal delivery. Methods: A prospective, randomized trial was conducted. Women scheduled for labor induction between 32 and 42 weeks and with unfavorable cervices (modified Bishop score 6 or lower) were randomized to receive oral misoprostol every 4 hours, up to four doses, with or without isosorbide mononitrate every 6 hours, up to two doses. A strict protocol was used, including timing of oxytocin use and amniotomy. Side effects were assessed 6 hours after study initiation. One hundred forty-two patients were required to detect a change in time to vaginal delivery of 4 hours (α=.05 and β=.20). Data were analyzed by intent to treat. Student's t, chi square, Fisher's exact, and Mann-Whitney tests were used where appropriate with P≤.05 deemed significant. Results: One hundred fifty-six women were randomized; three were excluded after randomization. Seventy-eight women received misoprostol, and 78 received misoprostol with isosorbide mononitrate. Demographic characteristics were similar between groups. The time to vaginal delivery was not reduced when isosorbide mononitrate was added to misoprostol. Cesarean delivery rates and contraction and fetal heart rate abnormalities were similar between groups. Side effects were also similar between groups, except that women given isosorbide mononitrate experienced headaches more often. Neonatal outcomes were similar between groups. Conclusion: The addition of vaginal isosorbide mononitrate to oral misoprostol for cervical ripening and labor induction did not reduce time to vaginal delivery and was associated with a greater incidence of headache.