Objectives: To compare the effectiveness of single-dose sublingual misoprostol to manual vacuum aspiration in the treatment of incomplete spontaneous abortion in Enugu, Nigeria.Design: Multi-centre randomized controlled trialSetting: A teaching hospital, the University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu and a private specialist hospital, Julius Memorial Specialist Hospital Enugu, Nigeria were used for the studyParticipants: In all, 212 consecutive consenting women with sonologically confirmed, first-trimester incomplete spontaneous abortion at the gynaecological emergency departments of the study centers were recruited but, 203 women completed the study and their results analysed.Intervention: Single-dose of sublingual misoprostol 400mcg with the participant followed-up at the gynecology clinic one week after with an ultrasound scan for the completeness of the uterine evacuation. Main outcomes measures: The primary outcome measure was the incidence of complete uterine evacuation (complete abortion) after one week of treatment while the secondary outcome measures included incidence, types, and tolerability of treatment side effects as well as participants’ satisfaction with the treatment receivedResults: Two hundred and three eligible women were randomised into the intervention group (n = 102) that received single-dose sublingual misoprostol 400mcg and the control group (n = 101) that received manual vacuum aspiration. Incidence of complete abortion was 86.3% for the misoprostol group and 100.0% for the control group, RR = 0.86, (CI 95%: 0.80 - 0.93), p <0.001. The most common side effect was abdominal pain with an incidence of 27.5% versus 48.55 for the misoprostol and control groups respectively (p = 0.002). Most participants in each group (81.1% versus 77.6% for the misoprostol and control groups respectively) considered the side effects as tolerable. The mean visual analogue scale score for maternal satisfaction was higher in the misoprostol group (86.7 ± 14.11) than the control group (81.36 ± 11.10), p < 0.001. Conclusions: The treatment of incomplete spontaneous abortion with single-dose sublingual misoprostol 400mcg produced a high rate of complete abortion among women in Enugu, Nigeria. Despite having a lower complete abortion rate, maternal satisfaction was higher when compared with women that had manual vacuum aspiration of the uterus. Trial registration: Trial registration number - PACTR202009857889210, date of registration - 23 September 2020. Retrospectively registered