Objective: The goal of this study was to evaluate oral mifepristone 24 hours prior to vaginal versus buccal misoprostol as cervical preparation prior to second-trimester dilation and evacuation. Study Design: Women desiring abortion between gestational ages 16 weeks 0 days and 20 weeks 6 days were randomized to 200-mg mifepristone 20-24 hours and 400-mcg vaginal or 400-mcg buccal misoprostol 1-2 hours prior to dilation and evacuation. Primary outcome was intraoperative procedure time defined as time of initial cervical dilation assessment to speculum out. Secondary outcomes included initial Pratt dilator accepted without resistance and participant and provider perceptions. The study was powered to detect a 4-minute difference in procedure time with 36 participants in each arm. Results: Of 72 women enrolled, 72 were randomized and 68 completed the study. Age, BMI, gestational age (mean 27.8 weeks, SD 6.5), and parity did not significantly differ. Total procedure times were 9.4 and 9.9 minutes in the vaginal and buccal groups, respectively, with difference of 0.5 (95% CI -1.65, 2.81). Initial Pratt dilation was 49 and 47 Fr in the vaginal and buccal groups, respectively, with difference of 2 Fr (95%CI -8.34, 1.62). Participant and provider perceptions did not differ. All 68 procedures were completed without hemorrhage, cervical laceration, or other observed complications. Conclusion: Mifepristone 24 hours prior to vaginal or buccal misoprostol is effective as cervical preparation 2 hours prior to dilation and evacuation at 16 weeks through 20 weeks 6 days. Implications: For dilation and evacuation at 16-20.6 weeks, mifepristone and vaginal misoprostol does not improve dilation or shorten procedure time significantly as compared to mifepristone and buccal misoprostol.