We examined whether leukocytosis is a negative prognostic factor in patients who underwent primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and, if so, determined whether it is associated with impaired myocardial perfusion. Previous studies have identified leukocytosis as a predictor of mortality in AMI. Whether this association holds in patients how have undergone primary PCI using contemporary pharmacotherapy and correlates with impaired myocardial perfusion is unknown. Clinical outcomes and reperfusion success, using Thrombolysis In Myocardial Infarction (TIMI) flow and myocardial blush grades, were examined according to tertiles of baseline leukocyte count in 1,268 patients who underwent primary PCI for AMI in the CADILLAC trial. Patients with higher leukocyte count were younger and more likely to be current smokers. Preprocedure TIMI grade 0 flow was more frequent in patients with higher leukocyte counts, but postprocedural TIMI grade 3 flow rates were equally high (>94%) in all 3 groups. Myocardial blush grade 2/3 was achieved at similar rates after PCI in patients with low, intermediate, and high baseline leukocyte counts (52.0% vs 51.5% vs 50.1%, p = 0.8). Higher baseline leukocyte counts were associated with greater myonecrosis (p <0.0001) and increased mortality at 1 year (2.7% vs 4.6% vs 5.4%, respectively, p = 0.047). By multivariate analysis, baseline leukocyte count (in increments of 1,000, hazard ratio 1.07, 95% confidence interval 1.02 to 1.10, p = 0.005) and peak creatine phosphokinase (hazard ratio 1.22, 95% confidence interval 1.14 to 1.29, p <0.001) were independent predictors of 1-year mortality. In conclusion, baseline leukocytosis is an independent correlate of larger infarct and increased mortality after primary PCI in AMI, an effect not explained by decreased myocardial perfusion.