Background-Our purposes were to estimate the strength of the longitudinal relationship between hyperinsulinemia and cardiovascular diseases (CVD) from the available literature and to identify study characteristics that modify this relationship. Methods and Results-Articles were identified by means of a MEDLINE and Embase search and citation tracking. Eligible studies were prospective population-based cohort studies and nested case-control studies on the relationship between, on the one hand, fasting or nonfasting insulin levels and, on the other hand, myocardial infarction, death from coronary heart disease, and/or ECG abnormalities. Data were extracted pertaining to insulin measurements, type of outcome studied, adjustment for confounding, sex, mean age of the study population, follow-up period, insulin assay, and ethnic background (white or nonwhite). Associations of insulin and CVD were reexpressed in a uniform manner, an estimate of relative risk (RR) and 95% CI, to be used in meta-regression analyses. Twelve of 17 potentially eligible articles provided sufficient information. Overall, a weak positive association was found. The meta-analysis resulted in an estimated summary RR (95% CI) of 1.18 (1.08 to 1.29) for differences in insulin level, equivalent to the difference between the 75th and the 25th percentiles of the general population in the Netherlands. Ethnic background and type of insulin assay modified the relationship between insulin and CVD with borderline significance. Conclusions-Hyperinsulinemia is a weak risk indicator for the occurrence of CVD. The relationship between hyperinsulinemia and CVD was modified by ethnic background and by the type of insulin assay involved. (Circulation. 1998;97:996-1001.)