Background Simultaneous oral mifepristone and vaginal misoprostol has a 24-h expulsion rate of approximately 90% when used for abortion through 63 days' gestation. This pilot study sought to determine if a simultaneous regimen using buccal misoprostol would be similarly effective and merit further investigation. Study design One hundred twenty women were enrolled into three equal groups by gestational age: ≤49 days (Group 1), 50–56 days (Group 2) and 57–63 days (Group 3). After swallowing 200 mg of mifepristone, subjects received 800 mcg buccal misoprostol. Participants returned in 24±1 h for evaluation of expulsion by ultrasonography. Women with a persistent gestational sac received 800 mcg vaginal misoprostol. Further follow-up occurred at 1, 2 and 5 weeks by telephone or in person, as appropriate. Sample sizes for each group were estimated with the aim of establishing a 24-h expulsion rate of 90% (95% CI=76–95). Results The 24-h expulsion rates for Groups 1, 2 and 3 were 73% (95% CI=56–85), 69% (95% CI=52–83) and 73% (95% CI=56–85), respectively. Common side effects were nausea (62%), vomiting (33%) and diarrhea (48%), which did not differ by gestational age. Forty-three percent of subjects found the taste of buccal misoprostol objectionable; 30% found buccal retention uncomfortable or inconvenient, and 10% reported oral irritation, sensitivity, numbness or oral ulcers. Conclusions Simultaneous oral mifepristone and buccal misoprostol had a lower-than-hypothesized expulsion rate at 24 h. Although overall success rates at 7 or 15 days could have been higher than those observed at 24 h, we believe that this regimen does not warrant further study.