BackgroundWaist circumference (WC), a representative of abdominal visceral fat, is strongly associated with cardiovascular disease (CVD) and its outcomes. We aimed to define body mass index (BMI)-specific WC thresholds as predictors of CVD and all-cause mortality.MethodsIn this prospective cohort study in the context of the Tehran Lipid and Glucose Study (TLGS), a total of 3344 men and 4068 women were followed up for 18 years. Based on BMI, the participants were categorized into three groups: BMI < 25, 25 < BMI < 30, and BMI > 30. In each BMI category, sex-specific WC thresholds were estimated by the maximum value of Youden’s index to predict based on incident CVD events and all-cause mortality prediction.ResultsOverall 667 and 463 CVD events (the incidence rate of 3.1 to 4.5 in men and 1.1 to 2.6 in women per 1,000 person-years within BMI categories) and 438 and 302 mortalities (the incidence rate of 2.1 to 2.7 in men and 1.2 to 1.4 in women per 1,000 person-years within BMI categories) were recorded in men and women, respectively. WC thresholds in the BMI categories of < 25, 25–30, and BMI > 30 kg/m2with regard to CVD events were 82, 95, and 103 cm in men and 82, 89, and 100 cm in women, and regarding all-cause mortality, the respective values were 88, 95, and 103 cm in men and 83, 90, and 99 cm among women.ConclusionBMI-specific WC thresholds observed here can help to better identify individuals at high risk of developing CVDs.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12889-023-16190-w.