Various risk factors and the multifactorial pathophysiology of cardiovascular disease (CVD) have been studied. We focused on the interaction between insulin resistance and inflammatory processes. Thus, we analyzed the association of triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio with subclinical inflammation and CVD risk in male smokers. We retrospectively reviewed medical records from the Health Promotion Center of Severance Hospital in Korea between 2015 and 2017. Subjects were currently smoking men aged 30 to 59, with leukocyte counts within the normal range, for a total of 1,566. We grouped participants into four groups using the median TG/HDL ratio and the median leukocyte count. The odds ratio (OR) of high Framingham 10-year CVD risk (≥10%) was calculated using multiple logistic regression. The median Framingham 10-year CVD risk increased significantly from Group 1 (low leukocyte count, low TG/HDL ratio) to Group 4 (high leukocyte count, high TG/HDL ratio). The OR for Group 4 was 2.46 compared with Group 1 after adjusting for various CVD risk factors. In subgroup analysis, the OR of the highest leukocyte group was 1.57 compared to the lowest leukocyte group after adjusting for other variables. In conclusion, TG/HDL ratio and subclinical inflammation were positively related to CVD risk in Korean male smokers.