ObjectiveTo evaluate the safety and efficacy of oral methotrexate and vaginal misoprostol for medical abortion.MethodsA prospective multicenter trial involved 300 women up to 49 days' gestation seeking elective abortion. Subjects received methotrexate 50 mg orally followed 5–6 days later by misoprostol 800 μg vaginally. The misoprostol dose was repeated if abortion did not occur.Resultscomplete abortion occurred in 273 of 299 women (91.3%;95% confidence interval [CI] 87.5, 94.2%); one woman was lost to follow-up. Abortion occurred within 8 days of the methotrexate in 233 women (77.9%;95% CI 72.8, 82.5%); the remaining 13.4% of women who aborted did so after a delay of 23.5 ± 9.8 days (median 23 days, range 10–45). Vaginal bleeding lasted an average of 15 and 11 days in immediate and delayed-success abortions, respectively. Complete abortion rates decreased linearly with increasing body surface area. After methotrexate and misoprostol administration, nausea was reported in 37% and 33%, vomiting in 11% and 18%, diarrhea in 12% and 18%, and subjective fever or chills in 15% and 31% of subjects, respectively.ConclusionOral methotrexate followed by vaginal misoprostol is effective for abortion and represents an acceptable alternative to intramuscular methotrexate in regimens for medical abortion.