ABSTRACT: OBJECTIVE:To summarize available data on the effectiveness and safety of single-agent misoprostol for medical abortion in the first trimester. DATA SOURCES:We searched MEDLINE, CABI, Cochrane, EMBASE, LILACS, the Web of Science, and ClinicalTrials.gov for English-language studies that evaluated misoprostol alone for abortion of a viable pregnancy in the first trimester. METHODS OF STUDY SELECTION:Our search yielded 1,562 citations, of which 38 included data from 53 trial groups that met our inclusion and exclusion criteria. TABULATION, INTEGRATION, AND RESULTS:We abstracted data about each trial group, including study characteristics, treatment regimen, clinical protocol, number of women treated and followed, and numbers with outcomes of interest. We used meta-analytic methods and logistic regression to examine factors associated with surgical intervention after treatment. Among all 12,829 evaluable women, 2,536 (meta-analytic estimate 22.0%, 95% CI 18.8-25.5%) had surgical uterine evacuation. Multiple factors were significantly associated with this proportion, including misoprostol amount per dose and route of administration, loss to follow-up rate, publication date, geographic region, number of misoprostol doses, duration of dosing, and time between dosing and evaluation. Of 6,359 evaluable women, 384 (meta-analytic estimate 6.8%, 95% CI 5.3-8.5%) had ongoing pregnancies. At most 26 of 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4-1.0%) were transfused or hospitalized for abortion-related reasons. In trials that provided satisfaction data, most women were satisfied or very satisfied with the treatment (meta-analytic estimate 78%, 95% CI 71-85%). CONCLUSIONS:Misoprostol alone is effective and safe and is a reasonable option for women seeking abortion in the first trimester. Research is indicated to further refine the regimen and to establish efficacy in the late first trimester. SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD42018083589.