Elevated plasma homocysteine (Hcy) is considered to be a risk factor of coronary artery disease (CAD), although this is still controversially discussed. This study investigated the role of Hcy in young patients with CAD in southern China. A total of 146 consecutive patients (aged a parts per thousand currency signaEuro parts per thousand 55 years) with angiographically proven CAD were enrolled in the study and 138 age-matched non-CAD individuals were included as the control group. Hcy levels were measured by enzymatic assay. Hyperhomocysteinemia (HHcy) was defined as Hcy a parts per thousand yenaEuro parts per thousand 15 A mu mol/l. A 10-year CAD risk was calculated using the Framingham risk score (FRS) modified according to the National Cholesterol Education Program Adult Treatment Panel III. There were significant differences between the CAD and control groups with regard to male sex (P < 0.01), smoking history (P < 0.05), and triglyceride levels (TG, P < 0.05), but no remarkable difference in other conventional risk factors (all P > 0.05). Hcy and high-sensitivity C-reactive protein (hs-CRP) levels were significantly higher in the CAD group than those in the control group (both P < 0.05). The FRS and estimated 10-year absolute CAD event risk were low in both groups and did not show a statistical difference. Multivariate logistic regression showed that male sex (odds ratio, OR, 3.68; 95 % confidence interval, 95 % CI, 1.54-10.01), smoking (OR, 2.54; 95 % CI, 1.15-5.36), TG (OR, 1.30; 95 % CI, 1.08-3.06), hs-CRP (OR, 3.74; 95 % CI, 1.72-12.21), and HHcy (OR, 2.03; 95 % CI, 1.26-5.83) were independently correlated with CAD in young patients. HHcy is an important independent risk factor for CAD in young patients in southern China after adjusting for other risk factors.