Background More information on the longitudinal care and outcomes of patients after myocardial infarction (MI) is needed to further improve the quality of MI care. The PREMIER study was designed to meet this need. Methods Patients with MI were prospectively screened and enrolled from 19 US centers between January 1, 2003, and June 28, 2004. Consenting patients had detailed chart abstractions of their medical history and processes of inpatient care, supplemented with a detailed, patient-centered interview. Centralized follow-up at 1, 6, and 12 months is being conducted to quantify patients' postdischarge care and outcomes, with a focus on their health status (symptoms, function, and quality of life). In 2003, detailed chart abstractions, devoid of all personal health information, were collected for patients eligible but not enrolled in PREMIER. Results Of 10 911 patients screened, 3953 were eligible and 2498 enrolled into PREMIER. Few clinically significant differences between the total MI population and those enrolled into PREMIER were observed. Adherence to accepted processes of quality care, such as aspirin and β-blockers on admission (96% and 91%) or discharge (96% and 93%), was high. One-month follow-up rates were high, with only 9% of patients being lost to follow-up. Conclusion PREMIER is a novel registry with detailed insights into patients' sociodemographic, clinical, and health status characteristics, as well as detailed monitoring of their inpatient and outpatient processes of care. Ultimately, PREMIER will describe patients' health status outcomes and identify determinants of these outcomes as an important step toward improving MI care.