Background—In experimental animals, iron overload appears to promote atherosclerosis and ischemic myocardial damage, but the results of epidemiological studies that relate iron stores to risk of coronary heart disease (CHD) have been inconsistent.

Methods and Results—We prospectively studied blood donations, which effectively reduce body iron stores, in relation to the risk of CHD among participants in the Health Professionals Follow-up Study. The lifetime history of blood donation was assessed with a questionnaire in 1992. The 38 244 men who were free of diagnosed cardiovascular disease at that time were included in the analyses. During 4 years of follow-up, we documented 328 nonfatal myocardial infarctions and 131 coronary deaths. Although the number of lifetime blood donations was strongly associated with lower plasma ferritin levels in a subsample, the blood donation was not associated with risk of myocardial infarction or fatal CHD. The age-adjusted relative risk (RR) of myocardial infarction for men in the highest category of blood donations (≥30) compared with never donors was 1.2 (95% CI 0.8 to 1.8), and this RR was not materially changed after adjustment for several coronary risk factors. No significant associations were found between blood donation and the risk of myocardial infarction in analyses restricted to men with hypercholesterolemia or those who never used antioxidant supplements or aspirin.

Conclusions—The study results do not support the hypothesis that reduced body iron stores lower CHD risk.