Hemoglobin (Hb) levels may interact with inflammatory activation, but it is unknown whether the interaction has any impact on clinical outcomes in acute coronary syndromes. The aim of this study was to assess the relationship between admission Hb levels, leukocytosis and clinical outcomes of ST-elevation myocardial infarction (STEMI) treated with primary angioplasty. Methods and Results The study group comprised 1,904 (1,380 men) patients with STEMI treated with primary percutaneous coronary intervention, enrolled in a prospective registry. The primary endpoint of in-hospital death occurred in 90 (4.7%) patients. According to univariate analysis, extreme values of Hb (for 1(st) and 5(th) vs mid quintiles respectively: hazard ratio (HR) =7.1, P<0.001 and HR =3.2, P=0.024) and leukocytosis above median (HR =2.09, P=0.001) significantly correlated with in-hospital death. After dividing patients into high and low white blood cell (WBC) count groups, a U-shaped relationship of Hb levels and mortality was observed for patients with higher leukocytosis (1(st) and 5(th) vs mid quintiles respectively: HR =8.1, P=0.001 and HR =4.4, P=0.022), whereas in patients with lower WBC count higher mortality was related solely to the lowest Hb quintile (HR =6.9, P=0.010 vs mid quintile). Conclusion Higher mortality associated with higher Hb levels in STEMI patients treated with primary angioplasty is limited to patients with increased leukocytosis.