Objective: To evaluate adjunctive misoprostol or mifepristone versus overnight osmotic dilators alone for cervical preparation before dilation and evacuation at 16-23+6/7 weeks. Methods: This double-blind, three arm multicenter randomized trial compared osmotic dilators alone, dilators plus 400 mcg of buccal misoprostol 3 hours preoperatively and dilators plus 200 mg of oral mifepristone during dilator placement for dilation and evacuation. Our primary outcome was operative time. Secondary outcomes included initial cervical dilation, dilation and evacuation completion on first attempt, need for mechanical dilation and complications. Three hundred women were required for 80% power to detect a 2 minute difference in operative time within two cohorts: 16-18 6/7 weeks (N=150) and 19-23 6/7 weeks gestation (N=150). Results: We found no difference in operative time between treatment arms in either gestational cohort. Adjusting for IUD insertions, total procedure time was shorter after mifepristone than dilators alone in the later cohort (9.4 min vs. 13.4 min, p=.007). Initial dilation was greater with misoprostol than dilators alone in the early cohort (2.4 vs. 2.0 cm, p=.007), but similar in the later cohort. More subjects in the dilators alone arm required additional dilation in the early cohort (35.3% vs. 9.8% misoprostol vs. 14.3% mifepristone, p=.003); but not the later cohort. We found no difference in procedure completion on the first attempt. Provider satisfaction with cervical preparation was highest after mifepristone (71.8% vs. 78.8% vs. 86.8%, p<.0001). There were no significant differences in complications. Conclusion: There may be benefit to adjunctive mifepristone or misoprostol for cervical preparation before dilation and evacuation, but benefits are modest.