Objective: To evaluate the effect of vaginal isosorbide mononitrate (IMN) plus oral hydration compared with oral hydration alone in improving the amniotic fluid index (AFI) and obstetric and perinatal outcomes in pregnancies complicated by isolated oligohydramnios (IO). Design: A randomized controlled trial. Setting: Obstetrics and Gynecology Department, Benha University Hospital. Materials and methods: The study included 210 singleton pregnancies (>28 gestational weeks) complicated by IO. Participants were scheduled into two equal groups. The study group received vaginal isosorbide mononitrate plus oral hydration and the control group received oral hydration plus placebo vaginal tablet. The amniotic fluid index was assessed at randomization, 24 h after treatment then weekly till delivery. Results: One-hundred participants completed the study in each group. A significant increase of AFI was detected 24 h after treatment in both groups. This effect did not continue for more than one week unless IMN was added. The mean AFI was significantly higher in IMN group at the final assessment. The IMN group had a significantly higher gestational age at the time of delivery, prolonged randomization delivery interval, a lower cesarean delivery rate, and their neonates were less likely to have low birth weight, low Apgar score, and admission to the neonatal intensive care unit. Neonatal deaths were reported in one case of the study group and 5 in the control group, and the difference was not significant. Conclusion: Nitric oxide donors may offer a promising choice in improving amniotic fluid volume and pregnancy outcomes in cases of isolated oligohydramnios.