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Objective: To explore the feasibility and diagnostic accuracy of modified subtraction coronary CT angiography (CCTA) with short breath-holding time in patients who have limited breath-hold capability and severe coronary artery calcification. Methods: 11 patients with a coronary calcium score >400 underwent CCTA using a modified subtraction protocol. All patients were unable to hold their breath for more than 20 s. Subjective image quality using a four-point scale and the presence of significant (>50%) luminal stenosis were assessed for each calcified or stented segment on both conventional CCTA and modified subtraction CCTA images and compared with invasive coronary angiography (ICA) as the gold standard. Results: The mean breath-holding time was 13.0 ± 0.9 s. A total of 35 calcified or stented coronary segments were evaluated. The average image quality was increased from 2.1 ± 0.9 with conventional CCTA to 3.1 ± 0.7 with subtraction CCTA (p < 0.001). The segment-based diagnostic accuracy for detecting significant stenosis according to ICA revealed an area under the receiver-operating characteristic curve of 0.722 for conventional CCTA and 0.892 for subtraction CCTA (p = 0.036). Conclusion: Modified subtraction CCTA allows the breath-holding time to be shortened to <15 s. As compared with conventional CCTA, modified subtraction CCTA showed improvement in image quality and diagnostic accuracy in patients with limited breath-hold capability and severe calcification. Advances in knowledge: Modified subtraction CCTA can improve the diagnostic accuracy in patients with a high calcium score and patients who are unable to perform long breath-holds. [ABSTRACT FROM AUTHOR]