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Objectives The association between hematocrit levels and the risk of cardiovascular disease (CVD) has been reported inconsistently. We aimed to investigate the association of hematocrit levels with the development of stroke and coronary heart disease (CHD) in a general Japanese population. Methods A total of 2585 community-dwelling Japanese individuals aged 40 years or older in 1988 were followed up for 19 years. These subjects were divided into four groups according to the sex-specific quartiles of hematocrit at baseline. Results During the follow-up, 301 subjects developed stroke (210 ischemic and 91 hemorrhagic) and 187 developed CHD. The risk of ischemic stroke was higher in both the lowest (Q1: men, ≤44.7%; women, ≤39.3%) and the highest (Q4: men, ≥49.7%; women, ≥43.8%) quartiles than in the third quartile (Q3: men, 47.1%–49.6%; women, 41.7%–43.7%) used as a reference (multivariable-adjusted hazard ratios [95% confidence intervals]: Q1, 1.55 [0.99–2.43]; Q2, 1.44 [0.93–2.23]; Q3, 1.00; and Q4, 1.62 [1.06–2.50]; P = 0.86 for trend). In contrast, hematocrit levels and the risk of hemorrhagic stroke showed a linear inverse association (Q1, 1.91 [1.03–3.54]; Q2, 1.26 [0.68–2.34]; Q3, 1.00; and Q4, 0.81 [0.41–1.61]; P = 0.009 for trend). The risk of CHD increased significantly in Q4 (Q1, 1.13 [0.71–1.80]; Q2, 1.08 [0.69–1.71]; Q3, 1.00; and Q4, 1.60 [1.04–2.46]; P = 0.13 for trend). Conclusions Our findings suggest that both elevated and decreased hematocrit levels are associated with an increased risk of CVD, but the influence of hematocrit is different among subtypes of CVD. [ABSTRACT FROM AUTHOR]