Background-The relationship between white blood cell count (WBCc) and mortality in patients with ST-segmentelevation acute myocardial infarction treated with percutaneous coronary intervention is poorly understood. Furthermore, whether there is a relationship between WBCc and risk of noncardiac mortality and bleeding after percutaneous coronary intervention is unknown. Methods and Results-The baseline WBCc was available in 3193 of 3345 patients (95.5%) who underwent percutaneous coronary intervention in the Harmonizing Outcome With Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial. In a propensity-adjusted multivariable analysis, WBCc was an independent predictor of 1-year cardiac mortality (hazard ratio, 1.15; 95% confidence interval, 1.09 to 1.22), noncardiac mortality (hazard ratio, 1.19; 95% confidence interval, 1.10 to 1.29), and major bleeding (hazard ratio, 1.08; 95% confidence interval, 1.04 to 1.12). After adjustment for baseline creatinine phosphokinase levels and left ventricular ejection fraction, WBCc remained an independent predictor of 1-year all-cause mortality and cardiac mortality. In patients matched for baseline creatinine phosphokinase levels at hospital admission, the median peak creatinine phosphokinase level was significantly higher in patients with high WBCc (Ͼ11 000 per 1 mm 3 ) compared with low WBCc (1851 U/L [range, 880-3307 U/L] versus 1241 U/L [range, 540 to 2,78], respectively; PϽ0.0001). In this subgroup of patients, WBCc was an independent correlate of peak creatinine phosphokinase level, and remained an independent predictor of 1-year mortality. Conclusions-In patients with ST-segment-elevation acute myocardial infarction undergoing percutaneous coronary intervention, elevated baseline WBCc is an independent predictor of infarct size, as assessed by peak creatinine phosphokinase level, and of 1-year cardiac mortality, noncardiac mortality, and major bleeding. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00433966.