A 10-year longitudinal population-based study, entitled the Isfahan Cohort Study (ICS) is being conducted. The ICS commenced in 2001, recruiting individuals aged 35+ living in urban and rural areas of three counties in central Iran, to determine the individual and combined impact of various risk factors on the incidence of cardiovascular events. After 24379 person-years of follow-up with a median follow-up of 4.8 years, we documented 219 incident cases of ischemic heart disease (IHD) (125 in men and 94 in women) and 57 incident cases of stroke (28 in men and 29 in women). The absolute risk of IHD was 8.9 (7.8-10.2) per 1000 person-years for all participants, 10.6 (8.8-12.5) per 1000 person-years for men and 7.4 (6.0-9.0) per 1000 person-years for women. The respective risk of ischemic stroke was 2.3 (1.7-3.0), 2.3 (1.6-3.3) and 2.3 (1.5-3.2) per 1000 person-years. The risk of IHD was approximately 3.5-fold higher in the presence of hypertension, followed by diabetes mellitus and hypercholesterolemia with near 2.5- and twofold higher risk, respectively. This cohort provides confirmatory evidence of the ethnic differences in the magnitude of the impact of various risk factors on cardiovascular events. The differences may be due to varying absolute risk levels among populations and the existing ethnic disparities for using western risk equations to local requirements.