Background: This study was designed to investigate the association between serum carbohydrate antigen 125 (CA125) and coronary artery calcification (CAC) score in patients without known coronary artery disease. Material/Methods: The study groups included 348 consecutive subjects with chest pain but without known coronary artery disease, and who underwent an estimation of CAC score in our hospital. Results: The clinical and Laboratory characteristics of all subjects are presented according to serum CA125 concentrations tertiles. The CAC score was found to be increased in the tertiles (31.6 +/- 82.10, 73.3 +/- 125.6, 122.9 +/- 135.9 U/mL, p<0.001). Serum CA125 concentrations are increased in calcium-positive patients compared with calcium-negative ones (9.3 +/- 4.79 vs. 11.2 +/- 7.36, p=0.003). A positive correlation between serum CA125 and CAC score was observed (r=0.319, p<0.001) in all participants. Similarly, the serum concentrations of CA125 were found to be positively correlated with CAC score in both women and men (r=0.328, p<0.001; r=0.265, p=0.001, respectively). Multiple linear regression analysis results indicated that serum CA125 concentrations are independently related to CAC score in the study population (beta=0.173, p=0.001), and age, sex, diabetes mellitus, and high-sensitivity C-reactive protein (hs-CRP) were also associated with CAC score in multiple linear regression analysis. Conclusions: Serum CA125 concentrations are correlated with CAC score in the population without known coronary artery disease, and serum CA125 may be considered as a marker to estimate CAC in the study population.