Elevated leukocyte count during ST-segment elevation myocardial infarction is associated with adverse clinical outcomes. Whether increased leukocyte count after primary percutaneous coronary intervention (PCI) directly reflects larger infarct size and left ventricular impairment is not known. The aim of this study was to assess the relation between leukocyte and neutrophil counts with infarct size and the left ventricular ejection fraction (LVEF) after primary PCI. Three hundred sixty-three patients from the Evaluation of MCC-135 for Left Ventricular Salvage in Acute Myocardial Infarction (EVOLVE) study, a randomized, double-blind, placebo-controlled trial assessing the efficacy of intracellular calcium modulator as an adjunct to primary PCI in patients with first ST-segment elevation myocardial infarctions, were evaluated. Total and differential leukocyte counts were measured before and serially after PCI. Infarct size and the LVEF were assessed using single-photon emission computed tomography after 5 and 30 days, and patients were followed up to 180 days. Total leukocyte and neutrophil counts obtained 24 hours after PCI were significantly correlated with infarct size (r = 0.34 and 0.37, respectively, p <0.001) and inversely correlated with the LVEF (r = −0.20 and −0.22, respectively, p <0.001). Patients with elevated leukocyte and neutrophil counts had larger infarct sizes (12.5% vs 5% and 13.5% vs 5%, respectively, p <0.001). The highest neutrophil quartile was associated with increased 180-day composite cardiac events (19% vs 20% vs 23% vs 45%, log-rank p <0.001). Elevated leukocyte and neutrophil counts independently predicted adverse cardiac events (hazard ratios 2.5 and 2.2, respectively, p = 0.001). In conclusion, elevated leukocyte and neutrophil counts after primary PCI in patients with ST-segment elevation myocardial infarctions are directly related to myocardial infarct size and the LVEF and are independent predictors of cardiovascular outcomes.