Background Iron has been suggested to play a role in the development of cardiovascular disease (CVD) through its pro-oxidant properties. However, epidemiological studies on iron status and the risk of CVD have yielded conflicting results. We therefore carried out a prospective study to evaluate the relationship between iron status and CVD in a middle-aged French population. Methods In total, 9917 subjects (3223 men aged 45–60 years and 6694 women aged 35–60 years) included in the SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) cohort were followed prospectively for 7.5 years. All cases of ischaemic heart disease (IHD) were identified and validated. CVD risk factors, haemoglobin and serum ferritin concentrations were measured at baseline. Findings Of men 4.3%, and of women 37.8%, presented at baseline a serum ferritin concentration <30 μg l −1 . During the follow-up, 187 subjects (148 men, 39 women) developed IHD. Serum ferritin was positively associated with total cholesterol, serum triglycerides, systolic and diastolic blood pressure, body mass index and haemoglobin. No linear association was found between serum ferritin and IHD risk in men or in women. Conclusion Our data do not support a major role of iron status in the development of IHD in a healthy general population.