We aimed to estimate the association of prophylactic antihemorrhagic medication use during dilation and evacuation (D&E) with operative hemorrhage and estimated blood loss (EBL). Records for all pregnant patients between 14 and less than 22 weeks of gestation who had a D&E procedure from January 2012 to December 2019 were retrospectively reviewed. Prophylactic antihemorrhagic medication use was defined as receiving vasoconstrictors, uterotonics, or both before identification of hemorrhage during a D&E procedure. Overall, 147 D&E procedures were completed at a mean of 16.4 (±2.2) weeks of gestation. Prophylactic medications were used in 72.1% (n=106) of D&E procedures. Prophylactic medication use was associated with lower operative hemorrhage (21.7% vs 51.2%, P < .01) and lower EBL (336.9 mL vs 551.3 mL, P < .01).