To investigate the clinical usefulness of subtraction coronary computed tomographic angiography (CCTA) in patients with severe calcification. A 320-row area detector CT system was used in this study. The subjects were 78 patients (47 men and 31 women, 739 years of age) with an Agatston score of >300 who were able to undergo prospective one-beat scanning during a single breath-hold. The CCTA findings were compared against invasive coronary angiography. The diagnostic capabilities of CCTA for the severely calcified segments with and without the additional information provided by subtraction CCTA were compared. Severe calcification was observed in 174 (31.9 %) of the 546 segments, and non-assessable regions were observed in 74 (13.6 %) of the segments. The addition of subtraction CCTA information improved the diagnostic accuracy for segments with severe calcification from 67.8 to 82.8 % on a per-segment basis and from 70.1 to 82.1 % on a per-patient basis, with non-assessable segments considered to be stenotic. When non-assessable segments were considered to be an incorrect diagnosis, the diagnostic accuracy was improved from 48.3 to 75.9 % on a per-segment basis and from 43.3 to 79.1 % on a per-patient basis. In addition, when evaluation was limited to non-assessable segments, subtraction CCTA provided a diagnostic accuracy of 81.1 % when non-assessable segments were considered to be stenotic or 66.2 % when non-assessable segments were considered to be an incorrect diagnosis. Subtraction CCTA improves the diagnostic capabilities of CCTA in patients with severe calcification.