Background The role of coronary calcification in cardiovascular events and plaque stabilization is still being debated, and factors involved in the progression of coronary calcification are not fully understood. This study aimed to identify the predictors for rapid progression of coronary calcification. Methods and Results Patients with serial optical coherence tomography imaging at baseline and at 6 months were selected. Changes in the calcification index and predictors for progression of calcification were studied. Calcification index was defined as the product of the mean calcification arc and calcification length. Rapid progression of calcification was defined as an increase in the calcification index above the median value. Among 187 patients who had serial optical coherence tomography imaging, 235 calcified plaques were identified in 105 patients (56.1%) at baseline. After 6 months, the calcification index increased in 95.3% of calcified plaques from 132.0 to 178.2 ( P <0.001). In multivariable analysis, diabetes mellitus (odds ratio [OR], 3.911; P <0.001), chronic kidney disease (OR, 2.432; P =0.037), lipid‐rich plaque (OR, 2.698; P =0.034), and macrophages (OR, 6.782; P <0.001) were found to be independent predictors for rapid progression of coronary calcification. Interestingly, rapid progression of calcification was associated with a significant reduction of inflammatory features (thin‐cap fibroatheroma; from 21.2% to 11.9%, P =0.003; macrophages; from 74.6% to 61.0%, P =0.001). Conclusions Diabetes mellitus, chronic kidney disease, lipid‐rich plaque, and macrophages were independent predictors for rapid progression of coronary calcification. Baseline vascular inflammation and subsequent stabilization may be related to rapid progression of calcification. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01110538.