Abstract Background Intrauterine growth restriction (IUGR) is associated with impaired placentation. Patients who are at risk of developing IUGR can be identified by abnormal umbilical artery Doppler at mid-trimester pregnancy. Nitric oxide (NO)-donors like isosorbide mononitrate reduce the impedance in the uteroplacental vessels and possess protecting effects on the endothelium. Objective To evaluate the efficacy and tolerability of Isosorbide Mononitrate therapy in reducing umbilical artery Doppler resistance index (RI) in pregnancies with fetal growth restriction. Patients and Methods This prospective randomized control trial was conducted at Obstetric Outpatient Clinic – Obstetrics and Gynaecology Department, Faculty of Medicine, Ain Shams University Maternity Hospitals from February 2021 until February 2022 and performed on women who attended ASUMH ECDU with IUGR. Results Finally, as regard side effects of isosorbide mononitrate therapy, our study reported that headache and overall side effects were statistically significant higher compared with control group. Conclusion Evident from the current study, nitric oxide (NO)-donors like isosorbide mononitrate had no prophylactic or therapeutic effects in management of pregnant cases associated with IUGR. It had no improving effect on umbilical artery Doppler or placental circulation. On the other hand it had unfavorable maternal adverse effects.