Background/Aims: Insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), and obesity often occur with type 2 diabetes. However, whether these risk factors of vascular disease lead to progression of atherosclerosis is unknown, independently of the diabetes status. The aim was to determine whether the combination of fatty liver, IR and obesity was associated with an increase in coronary artery calcium (CAC) score over time, regardless of diabetes status, other cardiovascular risk factors and medications. Methods: Data were analysed from a South Korean occupational cohort of 1035 people. The outcome was change in cardiac computed tomography (CT) CAC score between baseline and follow up. Ultrasound was used to define fatty liver and HOMA-IR≥75th centile defined IR. Hazard ratios (HR) [95% confidence intervals (CIs)] were estimated using Cox proportional hazards regression. Results: There were 279 (27.0%) participants whose CAC score increased from baseline (mean±SD age at baseline 44.3±5.2 years). CAC score of 756 subjects neither changed nor improved during follow up (mean±SD age 41.0±5.7 years). Prevalence of diabetes, fatty liver, HOMA-IR and obesity were all higher (all p＜0.001) in participants whose CAC score increased from baseline. Adjusting for diabetes and potential confounders, the combination of IR, fatty liver and obesity was independently associated with increase in CAC score over time [(HR 2.32, (95% CIs 1.41,3.79)]. Conclusions: The combination of fatty liver, IR and obesity is associated with progression of atherosclerosis over time, independently of diabetes, cardiovascular risk factors, and all medications for cardiovascular disease and diabetes.