Background— Leukocyte concentration in blood is a classical marker of systemic inflammation. Whether high leukocyte counts are associated with incidence of heart failure (HF) is unknown. This population-based study explored whether the leukocyte concentrations were associated with incidence of hospitalizations due to HF. Methods and results— Leukocyte counts were measured in 16 940 men from the general population (mean age 44 years) without history of myocardial infarction or stroke. Incidence of hospitalizations due to HF (primary diagnosis) was monitored over 23 years of follow-up, in relation to quartiles of leukocytes. Subjects with myocardial infarction during follow-up were censored in the main analysis. During the follow-up, 436 men were hospitalized due to HF. Incidence of HF hospitalizations was increased in men with high leukocyte counts. After adjustments for confounding factors, the adjusted hazards ratio (HR, 95% CI) for HF hospitalization was 1.00 (reference), 1.26 (0.93 to 1.7), 1.24 (0.91 to 1.7), and 1.73 (1.3 to 2.3), respectively, for men with leukocytes in the 1st, 2nd, 3rd, and 4th (highest) quartiles (trend, P <0.001). This relationship was consistent in smokers and nonsmokers and in men with and without hypertension, respectively. Conclusion— High leukocyte counts in middle-aged men were associated with increased long-term incidence of HF hospitalizations.