OBJECTIVE The association of total and high-density lipoprotein (HDL) cholesterol with stroke risk is unclear, especially regarding hemorrhagic stroke. METHODS We prospectively investigated the associations of serum total and HDL cholesterol and total/HDL cholesterol ratio with total and type-specific stroke incidence among 58,235 Finnish people aged 25 to 74 years and free of coronary heart disease and stroke at baseline. RESULTS During a mean follow-up period of 20.1 years, 3914 participants developed stroke events (3085 ischemic, 497 intracerebral hemorrhage, and 332 subarachnoid hemorrhage). The multivariable-adjusted hazard ratios at different levels of total cholesterol (<5 [reference], 5-5.9, 6-6.0, ≥7.0 mmol/L) were 1.00, 1.05, 1.16, and 1.22 for total stroke (Ptrend=0.036) and 1.00, 1.06, 1.19, and 1.27 for ischemic stroke (Ptrend=0.02) in men and 1.00, 0.58, 0.61, and 0.50 for intracerebral hemorrhagic stroke (Ptrend=0.02) in women, respectively. Low levels of HDL cholesterol and high total/HDL cholesterol ratio were associated with increased risks of total and ischemic stroke in both men and women. These associations disappeared in men but remained significant in women after further adjustment for body mass index, blood pressure, and history of diabetes. CONCLUSIONS The study showed a positive association between total cholesterol and total and ischemic stroke risks in men and an inverse association between total cholesterol and intrahemorrhagic stroke risk in women. The inverse association of HDL cholesterol and a positive association of total/HDL cholesterol ratio with total and ischemic stroke risks were found in men and women. These associations attenuated after adjustment for body mass index, blood pressure, and history of diabetes.