Adherence to evidence-based interventions for hospitalized cardiovascular disease patients is not optimal. This study assesses the impact of a national quality improvement program on adherence to guidelines in these patients. Data from 92 hospitals from across the United States participating in the Get With The Guidelines program for at least 1 year for 11 acute and secondary prevention measures from a preintervention baseline period and the subsequent 4 quarters of a quality improvement intervention were analyzed. A patient group of 45,988 patients with acute myocardial infarction, unstable angina, revascularization, or peripheral vascular disease was included in this evaluation. Significant improvement from baseline was seen in 10 of 11 measures by the fourth quarter: use of early aspirin for acute myocardial infarction, 76.4% to 88.0% (P < 0.0001); early beta-blocker for acute myocardial infarction, 64.4% to 79.5% (P < 0.0001); beta-blocker at discharge, 75% to 82.1% (P < 0.0001); smoking cessation counseling, 58.7% to 74.3% (P < 0.0001); angiotensin-converting enzyme inhibitor use for acute myocardial infarction, 64.5% to 69.9% (P < 0.0001); lipid treatment, 58.5% to 63.4% (P < 0.0001); lipid treatment for low-density lipoprotein > or =100 mg/dL, 60.4% to 67.0% (P < 0.0001); low-density-lipoprotein measurement, 48.8% to 53.2% (P < 0.0001); discharge blood pressure <140/90 mm Hg, 65.9% to 68.0% (P = 0.03); and referral to cardiac rehabilitation or exercise counseling, 65.0% to 88.3% (P < 0.001). Discharge aspirin use at 89.9% did not change. Statistically and clinically significant improvement in 10 of 11 quality-improvement measures for the treatment of patients hospitalized for cardiovascular disease was seen in hospitals participating in Get With The Guidelines.