Background: Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD. Methods: This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011-2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline. Results: Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17-1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01-1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71-1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77-2.14) or former smokers (HR, 1.22; 95% CI, 0.66-2.28). Conclusions: Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking.