OBJECTIVE To compare blood loss, efficiency, and acceptability of repeated doses of sublingual misoprostol with the standard Tunisian regimen of mifepristone-misoprostol for first trimester medical abortion. METHODS A prospective randomized trial of 252 healthy pregnant women requesting medical abortion in the first trimester (up to 56 days). Participants were randomized to receive 200mg of oral mifepristone followed by 400 microg of oral misoprostol (group 1) or 800 microg of sublingual misoprostol repeated every 4 hours for up to a maximum of 3 doses (group 2). Primary outcome was blood loss assessed by decrease in hematocrit. RESULTS Mean decrease in hematocrit at follow-up was significantly greater in group 1 than in group 2 (3.65%+/-1.18% vs 2.69%+/-1.89%, respectively; P=0.02). There was no difference in efficiency rates between groups 1 and 2 (94.5% vs 92.1%; P=0.7). Comparable proportions of women experiencing at least one adverse effect after misoprostol administration were reported in groups 1 and 2 (81.7% vs 79.4%; P=0.75). CONCLUSIONS Compared with the most widely used regimen in Tunisia (mifepristone-misoprostol), sublingual misoprostol alone induces less blood loss (although not clinically significant); it is less expensive and offers reduced interval time to expulsion.