Coronary Artery Disease (CAD) is the number one killer of adults in the Iran. Fibrinogen is CAD risk factor that participation in both the atherogenic and thrombogenic processes. Also playing a role in thrombosis and atherogenesis is Homocysteine, as a risk factor for CAD.Long-term exercise training and physical activity favorably modified several of the conventional CAD risk factors. No such association has been consistently shown between regular physical activity and exercise training with fibrinogen and homocysteine concentrations and the effects of physical activity and exercises training on fibrinogen and homocysteine were not clear. This study aimed to clarify whether long-term aerobic exercise training and physical activity reduced fibrinogen and homocysteine levels in men.This cross-sectional study involved 45 voluntary participants that divided into three groups of 15 each, as follows: active, sedentary, and CAD group. Fasting whole blood samples were collected from the left antecubital vein after 9-12 hours of fasting.The serum concentrations of fibrinogen were measured using the chronometric method. Enzyme-linked immune sorbent assay (ELISA) was used to measure the serum concentrations of homocysteine by Biomerio fully automated analyzer. Between-group comparisons of estimated VO2max, homocysteine, and fibrinogen were performed using one-way analysis of variance (ANOVA) and the LSD Post Hoc test. Significant levels for all tests were set at p≤0.05. No significant between-group differences were found in the serum concentrations of homocysteine [F (2, 42) =0.107, p=0.898] and the serum concentrations of fibrinogen [F (2, 42) = 0.468, p=0.630]. Significant differences of estimated VO2max were found between active and sedentary groups (p≤0.001), and active and CAD groups (p≤0.001). The results indicated that exercise training and physical activity does not have any desirable effects on the serum levels of homocysteine and fibrinogen. Hence, more studies are needed to clarify the effects of physical activity and exercise training on homocysteine and fibrinogen levels. More studies are required to clarify the optimal intensity, duration, and type of exercise to favorably modify these risk factors of CAD.