BACKGROUND: Manual vacuum aspiration is a safe and effective technology for the treatment of incomplete miscarriage but it is not widely available and affordable in rural areas particularly in low-resource countries. Misoprostol is an alternative to manual vacuum aspiration for the treatment of incomplete miscarriage. AIM: To compare the effectiveness, client acceptability and satisfaction, and cost-effectiveness of misoprostol with manual vacuum aspiration for the treatment of the first-trimester incomplete miscarriage. SUBJECTS AND METHODS: This study was conducted between February 1, 2018 and August 31, 2018 at Alex Ekwueme Federal University Teaching Hospital Abakaliki, Nigeria. 100 participants were randomized to treatment with either manual vacuum aspiration or 600 µg oral misoprostol. The main outcome measures assessed at 1-week follow-up were complete uterine evacuation, client acceptability and satisfaction, and cost-effectiveness. Data were analyzed using SPSS version 25. Sociodemographic characteristics, treatment outcomes and other variables were summarized by descriptive statistics. Chi-square test was used for comparison between groups as regard categorical data while Student's't' test was used for comparison between groups for continuous data. P value of <0.05 was regarded as statistically significant. RESULTS: There was a higher failure rate in the misoprostol arm when compared with MVA. Although this difference in complete uterine evacuation rate did not reach statistical significance (81.3% versus 95.7%, RR = 4.3, 95% CI 0.98-18.9, P value = 0.05), more participants in the misoprostol arm would choose the method again when compared with women in the MVA group (47 versus 30, X[2] = 16.95, P < 0.001). The mean client satisfaction score was significantly higher among women in the misoprostol arm compared to MVA group (13.2 (2.1) versus 7.3 (4.6), P < 0.001). The mean cost of primary treatment was higher in the MVA group compared with misoprostol arm ($67.8 (8.9) versus 14.4 (4.0), P < 0.001). There was no significant difference in the mean cost of repeat uterine evacuation in both study arms (MVA, $64.9 (6.3) versus misoprostol, $65.76 (6.6), P = 0.86). CONCLUSION: Although medical treatment was associated with a higher failure rate, there was no statistically significant difference in the effectiveness of both treatment methods. However, medical treatment was associated with higher client acceptance and satisfaction and was more cost-effective than surgical treatment.