Missed miscarriages, occurring in upto 15% of all clinically recognized pregnancies are a cause of concern for the patients. Though many researchers in the past have compared the surgical and medical approaches in management of such patients, only a few have executed an appraisal of two routes of misoprostol at equal dosages in treatment of first trimester missed miscarriages. To compare the efficacy of misoprostol by vaginal and oral route, for the management of first trimester missed abortion; and to recognize the utility of misoprostol for cervical dilation prior to any surgical termination of pregnancy. A randomized prospective trial, comparing the efficacy of misoprostol, by vaginal and oral routes, for termination of first trimester missed abortion was conducted in the Department of Obstetrics and Gynecology, Government Multi-Specialty Hospital, Chandigarh over one year. Hundred subjects satisfying the inclusion criteria from 213 consecutive women presenting to the institute with first trimester missed abortion were hospitalized. The study participants were randomly assigned to one of the two treatment groups, using sequentially numbered envelopes, to receive 400mcg misoprostol vaginally or orally to a maximum of three doses six hours apart, and outcome documented. Patients were followed up on Day 14 and 6 weeks after discharge. Primary outcome evaluated was drug-induced complete expulsion of Products of Conception (POCs). Secondary outcomes measured were induction expulsion interval, number of doses required, classification of failures, cervical canal permeability in women requiring surgical evacuation, side effects, hemoglobin drop, duration and amount of post-abortal bleeding, time of resumption of menses, experience with side effects, patient satisfaction and acceptability to treatment. Both routes were highly effective (vaginal=92%, oral= 74%, p=0.032), safe and acceptable with tolerable side effects. The mean time to expulsion was longer (13.24hrs) in the oral than vaginal group (10.87hrs). All 4 unsuccessful cases in vaginal group and 12 of 13 in oral group had permeable cervices prior to surgical evacuation. Most women labeled the side effects as tolerable in both the groups. Overall acceptance rate to treatment was high in both the groups A and B (76% and 70%). Vaginal misoprostol is more effective than oral misoprostol for first trimester missed abortion.