Objective: Elevated serum gamma-glutamyltransferase (GGT) has been demonstrated to be associated with coronary artery calcification (CAC). CAC progression is an important marker of atherosclerosis and correlates with future cardiovascular risk. However, there is a lack of research that directly examines the association between serum GGT and CAC progression. The aim of this study was to elucidate the association between serum GGT activity and CAC progression. Methods: We enrolled 1249 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. To eliminate the dependence of the interscan variability on the baseline CAC scores, square root-transformed CAC scores were used to analyze CAC progression. In addition, the annualized rate of change in CAC scoreswas computed. Results: Serum GGT activities were significantly higher in “progressors” than “non progressors”. The prevalence of progression increased with the GGT tertile (11.9%, 20.3% and 27.9% in the 1st, 2nd, and 3rd GGT tertiles, respectively; P < 0.001). In the multivariate logistic regression analysis, the odds ratio (95% confidence interval) for CAC score progression was 2.17 (1.33-3.53) in the highest GGT tertile group. By multivariate linear regression analysis, baseline serum GGT activity demonstrated a positive association with the annualized change in CAC score (β = 0.002; P = 0.012) after adjusting for cardiovascular risk factors. Conclusion: Elevated serum GGT levels are independently associated with CAC progression. Serum GGT levels may be a potential biomarker of future coronary atherosclerosis and prognosis.