Cardiovascular diseases (CVDs) are leading cause of morbidity and mortality and early identification of risk factors can help reduce mortality from them. The aim of this study was to determine the risk of CVD based on the Framingham Risk Score (FRS) among office workers, Yasuj City, Southwestern Iran. In this descriptive study, 180 workers aged 30-74 years old free of cardiovascular disease were recruited by single-stage stratified cluster sampling from the office of Yasuj City. Analysis showed that 163 workers (90.5%) were at low risk, 12 people (6.6%) at moderate risk, and five people (2.9%) at high 10-year risk of CVD. Mean of FRS and 10-year prediction of CVD risk was significantly higher among male workers than females. Subjects with normal body mass index than overweight and obese people had only significantly lower FRS (P <0.001), but 10-year risk of CVD did not differ among groups. Participants with Master of Science and above educational degree and subjects with normal waist-to-hip ratio had only significantly lower 10-year risk of CVD (P < 0.001). Nonsmokers, whose with systolic blood pressure <140 mm Hg, total cholesterol <240 mg/dL, normal total cholesterol/high-density lipoprotein-cholesterol (HDL-C), and abnormal HDL-C had significantly lower both FRS and 10-year CVD risk (P <0.01). This population-based study will health care policy makers develop targeted strategies to develop individual and community-based health care promotion programs.