BACKGROUND Labor induction in the presence of unfavorable cervix is a common indication for the use of prostaglandins. However, in the last years, there has been a considerable interest in the use of nitrous oxide donors for cervical ripening and labor induction. OBJECTIVE To evaluate the efficacy and safety of intravaginal administration of NOD isosorbide mononitrate (IMN) plus misoprostol versus misoprostol alone for cervical ripening and induction of labor. METHODS Department of Obstetrics and Gynecology, Woman's Health Center, Assiut University. METHODS Two hundred and ninety women scheduled for labor induction were recruited and assigned randomly to IMN or placebo followed by misoprostol 50 μg. The efficacy of the medication was evaluated by predetermined outcome variables for cervical ripening and induction of labor and delivery. RESULTS The two groups were comparable with respect to age, parity, gestational age, indication for induction, and Bishop's score. Women receiving IMN plus misoprostol showed significant changes in the Bishop score 6 h after administration as compared to misoprostol plus placebo (8.57 ± 1.46 vs. 7.6 ± 1.39 h, P = 0.001), significantly shorter intervals from the beginning of the induction to the beginning of the active phase of labor (10.97 ± 2.87 vs. 13.91 ± 2.16 h, P = 0.0004) and from the beginning of induction to the time of delivery (19.56 ± 3.96 vs. 23 ± 2.62 P ≤ 0.001). No significant differences in the incidence of uterine hypersystole, tachysystole and hyperstimulation. Regarding headache, much more women suffer headache in the IMN group (51) with significant difference to placebo group (11). CONCLUSIONS Using a combination of IMN and misoprostol is more efficient than misoprostol alone in terms of fast cervical ripening and shortening of induction-labour interval.