Background The aim of this study was to investigate the association of dietary insulin index (II), insulin load (IL), glycemic index (GI), and glycemic load (GL) with risk of cardiovascular disease (CVD) outcomes among adults. Methods This cohort study was conducted within the framework of the Tehran Lipid and Glucose Study on 2198 subjects, aged ≥19 years, who were followed-up for a mean of 4.7 years. Dietary GI, GL, II, IL were calculated using a food frequency questionnaire at baseline. Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across quartiles of dietary insulin and glycemic indices. Results Mean±SD age of the study population (44.9% men) was 38.3±13.4 years. During an average of 2406 ± 417 person-years of follow-up, 76 (3.5%) new cases of CVD were ascertained. The Mean±SD of II, IL, GI, and GL of participants were 51.7±6.5, 235.8±90.2, 61.9±7.8, and 202.2±78.1, respectively. After adjusting for age, sex, smoking, physical activity, daily energy intake, body mass index, diabetes, and hypertension, the hazard ratio (HR) of the highest quartile of dietary GL was 2.77 (95%CI:1.00-7.69, P for trend:0.033) compared with the lowest one. However, there was no significant association between dietary GI, II, IL and risk for CVD incident. Conclusions Our findings suggest that high GL diet can increase the incidence of CVD, whereas high dietary II and IL was not associated with risk of CVD among adults.