An elevated white blood cell (WBC) count at the time of hospital presentation is associated with increased mortality after acute myocardial infarction (AMI). The association between WBC count and the development of clinically significant complications of AMI and death during hospitalization for AMI is, however, less clear. The objectives of this observational study were to examine the association between baseline WBC count, the development of heart failure, cardiogenic shock, and death during hospitalization for AMI from a more generalizable community-wide perspective. The study sample consisted of adult residents of all ages from the Worcester, Massachusetts, metropolitan area (1990 census estimate 437,000) hospitalized with confirmed AMI at all greater Worcester medical centers. The study population consisted of 3,796 men and 2,734 women of all ages hospitalized with validated AMI, in 12 annual periods between 1986 and 1999, aggregated into quintiles based on WBC count obtained at the time of hospital admission. In multivariable-adjusted regression analyses controlling for potentially confounding demographic and clinical factors, patients in the uppermost quintiles of WBC count were at increased risk for heart failure (odds ratio [OR] 2.77, 95% confidence interval [CI] 2.33 to 3.31), cardiogenic shock (OR 2.82, 95% CI 2.05 to 3.87), and hospital death (OR 2.14, 95% CI 1.66 to 2.76). The results of our large observational study suggest that the peripheral total leukocyte count is strongly associated with the development of heart failure, cardiogenic shock, and death during hospitalization for AMI. These findings suggest that the WBC count should be considered an important prognostic factor associated with adverse hospital outcomes in patients with AMI.