This study aims to evaluate buccal misoprostol as an adjunct to synthetic osmotic dilators for same-day dilation and evacuation (D&E). A randomized, double-blinded, placebo-controlled trial of women 16 0/7 to 20 6/7 weeks gestation desiring D&E was used. Participants received synthetic osmotic cervical dilators (Dilapan-S®) at least 4 h prior to D&E and were randomized to 400mcg buccal misoprostol or placebo 3 h preoperatively, stratified by gestational age. The primary outcome was operative time with 36 participants needed to detect a 4-min difference (two-sided α=0.05, 80% power). Secondary outcomes included total procedure time, patient and provider acceptability, baseline cervical dilation and complications. Twenty-nine women were enrolled (misoprostol n=14, placebo n=15) and mean operative time was similar between the groups (11.1 vs. 13.5 min, respectively, p=.17). Complications were nonsignificantly more common for participants ≥19 weeks compared to <19 weeks (22% vs. 9%, p=.62) and those who received placebo compared to misoprostol (27% vs. 7%, p=.33). Two serious adverse events in the placebo group prompted early study closure for safety and futility. Placebo participants had longer overall procedure times (24 vs. 18 min, p=.03) and less cramping preoperatively (p<.01) but similar results for other secondary outcomes compared to those receiving misoprostol. Women strongly preferred same-day cervical preparation (98%). Adjunctive buccal misoprostol may not decrease operative times but may decrease complications when combined with synthetic osmotic dilators for cervical preparation for same-day D&E procedures. Although the trial was halted early and underpowered to make conclusions about the primary outcome, complication frequency and type warrant caution for use of synthetic osmotic dilators alone for cervical preparation for same-day D&E at ≥19 weeks gestation.