Background: Depression is a stronger predictor for the onset of or death from clinical coronary artery disease than traditional cardiovascular risk factors. The association between depression and coronary artery disease has previously been investigated in non-contrast enhanced computed tomography studies with conflicting results. The aim of this study was to further elucidate the depression-coronary artery disease relation by use of coronary computed tomography angiography. Methods: The calcified and noncalcified coronary plaque volumes were determined by semiautomatic volumetric quantification in 28 patients with late-onset major depression and 27 controls. The calcified plaque proportion, i.e., the calcified plaque volume divided by the total plaque volume, was used to assess the plaque composition. Results: There was no statistically significant difference in the total (p = 0.48), calcified (p = 0.15), and noncalcified (p = 0.62) plaque volume between patients and controls, and the total plaque volume did not predict depression, odds ratio = 1.001 [95% confidence interval: 0.999-1.003; p = 0.23]. However, the calcified plaque proportion was twice as high in patients compared with controls (14% vs. 7%, p = 0.044). Correspondingly, having depression was associated with an increased calcified plaque proportion of 11.3 [95% confidence interval: 2.63-20.1; p = 0.012] percentage points after adjustment for demographics and cardiovascular risk factors. Conclusion: The proportion of the total coronary plaque volume that was calcified was significantly higher in patients with late-onset major depression than in controls, indicating a difference in plaque composition.