A prospective observational study was conducted in 2,007 patients experiencing chest pain to determine impact of local quality improvement (QI) measures on the use of glycoprotein (GP) IIb/IIIa inhibitors in the ED treatment of high-risk patients with non-ST-segment elevation acute coronary syndromes (ACS). Patients with injury on the initial ECG or new sustained injury on continuous ECG were excluded. QI interventions were as follows: control (0-4 mo): no interventions (standardized protocols and prewritten orders in place 4 months prior); phase I (5-8 mo): simple education/awareness program with posted drug information pamphlets and eligibility criteria; phase II (9-12 mo): mandated QI form with real-time feedback and focused one-on-one physician education championed by an ED physician QI advocate. A total of 179 (8.9%) of the study patients met predefined high-risk criteria. Of these, a total of 41 (23.0%) patients had GP IIb/IIIa inhibitor therapy initiated in the ED. Percent of high-risk patients receiving therapy increased from 6.0% during the control phase to 16.1% during phase I and 50.9% during phase II. After controlling for patient demographics, patients treated during phase I had a 2.8 times increased odds (95% confidence interval CI: 0.8-10.3; P = .11 [not significant]) of receiving GP IIb/IIIa inhibitor relative to the control phase, and patients treated during phase II had a 20.2 times increased odds (95% CI: 6.1-66.9; P <.0001) of treatment. In conclusion, local QI measures incorporating standardized protocols, preprinted orders, physician education, and interactive feedback championed by an ED QI physician advocate can increase early use of GP IIb/IIIa inhibitors in the ED treatment of high-risk patients presenting with chest pain.