BACKGROUND: Coronary artery calcification is a significant contributor to reduced accuracy of coronary computed tomographic angiography (CTA) in the assessment of coronary artery disease severity. The aim of the current study is to assess the impact of a prototype calcium deblooming algorithm on the diagnostic accuracy of CTA. METHODS: 40 patients referred for invasive catheter angiography underwent CTA and invasive catheter angiography. The CTA were reconstructed using a standard soft tissue kernel (CTASTAND) and a deblooming algorithm (CTADEBLOOM). CTA studies were read with and without the deblooming algorithm blinded to the invasive coronary angiogram findings. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value for the detection of stenosis ≥50% or ≥70% were evaluated using quantitative coronary angiography as the reference standard. Image quality was assessed using a 5-point scale, and the presence of image artifact recorded. RESULTS: All studies were diagnostic with 548 segments available for evaluation. Image score was 3.64 ± 0.72 with CTADEBLOOM, versus 3.56 ± 0.72 with CTASTAND (p = 0.38). CTADEBLOOM had significantly less calcium blooming artifact than CTASTAND (12.5% vs. 47.5%, p = 0.001). Based on a 50% stenosis threshold for defining significant disease, the Sensitivity/Specificity/PPV/NPV/Accuracy were 65.9/84.9/27.6/96.6/83.4 for CTADEBLOOM and 75.0/81.9/26.6/97.4/81.4 for CTASTAND using a ≥50% threshold. CTADEBLOOM specificity was significantly higher than CTASTAND (84.9% vs. 81.5%, p = 0.03), with no difference between the algorithms in sensitivity (p = 0.22), or accuracy (p = 0.15). These results remained unchanged when a stenosis threshold of ≥70% was used. Interobserver agreement was fair with both techniques (CTADEBLOOM k = 0.38, CTASTAND k = 0.37). CONCLUSION: In this proof of concept study, coronary calcification deblooming using a prototype post-processing algorithm is feasible and reduces calcium blooming with an improvement of the specificity of the CTA exam.