A retrospective cohort analysis was conducted on patients who underwent percutaneous coronary intervention (PCI) before and after a practice change which reduced the infusion duration of eptifibatide from 18 hours to the time required for completion of a single vial of 75 mg initiated during PCI. Primary end points were inhospital cardiovascular events, target vessel revascularization, and major or minor bleeding. The secondary end point was drug cost. A total of 1,647 patients received the standard-duration infusion (18 hours), and 1,237 received the short-duration infusion. The median infusion times were 18.1 hours (interquartile range 17.7 to 18.7) and 6.6 hours (interquartile range 5.6 to 11.3) in the standard- and short-duration groups, respectively. No differences were found for the rate of inhospital cardiovascular events (2.0% vs 1.9%, respectively; p = 0.78) or inhospital revascularization (0.2% vs 0.3%, respectively; p = 0.68). Also, no statistically significant difference was observed in major bleeding (standard 4.3% vs short 4.4%; p = 0.94) or minor bleeding (standard 3.3% vs short 2.3%; p = 0.09). In conclusion, using a shortened infusion reduced eptifibatide use by an average of 1.6 vials at cost savings of $823 per patient and resulted in no difference in inhospital cardiovascular events, revascularization, or bleeding.