Aim: Serum albumin and globulin have important roles in atherosclerosis development; however, separate studies exploring the relationship between albumin or globulin and coronary heart disease (CHD) have been conducted. We explored whether there was a synergistic effect of albumin and globulin on the presence of CHD. Methods: A total of 395 patients aged 50-74 years with angiographically documented CHD were recruited, and 596 age-and sex-matched controls without CHD were randomly selected from the general population. The association of albumin and globulin with CHD was analyzed using conditional logistic regression after adjusting for traditional CHD risk factors. Results: Mean values of serum albumin and globulin were significantly lower in cases than in controls (p<0.001). In the fully adjusted model, compared with participants whose albumin (>= 47.3 g/L) and globulin (>= 25.6 g/L) levels were both higher than the median levels in these participants, the odds ratio for CHD was 1.59 (p=0.048) for participants with higher albumin (>= 47.3 g/L) but lower globulin (<25.6 g/L), 2.79 (p<0.001) for participants with lower albumin (<47.3 g/L) but higher globulin (>= 25.6 g/L), and 16.03 (p<0.001) for participants with lower levels of both albumin (<47.3 g/L) and globulin (<25.6 g/L). Conclusions: Low serum albumin and globulin are independently associated with CHD. The synergistic association of both low albumin and low globulin with CHD is greater than either one alone. The synergistic effect deserves further investigation.