Introduction: People living with HIV (PLWH) have more subclinical cardiovascular disease than people without HIV (PWOH), but few studies have evaluated risk for mortality based on coronary artery calcium (CAC) among this population. Purpose: This study aimed to determine the association between CAC and all-cause mortality among male PLWH and PWOH and to identify a potential interaction with HIV serostatus. Methods: The study population was derived from the MACS, a US prospective observational cohort study including male PLWH and PWOH. Participants underwent cardiac non-contrast computed tomography from July 2004 to November 2013. Men with atrial fibrillation, coronary heart disease, or coronary revascularization were excluded. Cox proportional hazards model was used to calculate adjusted hazard ratios [aHR] for all-cause mortality among men with vs. without baseline CAC (Agatston score>0) and per standard deviation (SD) increment in continuous Agatston score [log (CAC+1)], controlling for demographic and cardiac risk factors. CAC differences by HIV serostatus were evaluated using multiplicative CACхHIV interaction terms. Results: Among 1344 males (mean age 50 years, CAC prevalence 46%, 823 (61%) PLWH), we observed 110 deaths (13%) among PLWH and 41 deaths (8%) among PWOH during the follow-up period (median: 13.4 years). Among PLWH, 62% had an undetectable plasma HIV viral load, the median CD4 cell nadir was 284 cells/μL, and 17% had a history of clinical AIDS. The age-adjusted mortality rate was 13.5 (95% CI: 11.0-16.5) among PLWH and 7.8 (5.4-10.9) among PWOH per 1000 person-years. CAC presence was associated with all-cause mortality among all participants (aHR=1.47, 95% CI: 1.02-2.11, p=0.04), and among PLWH (aHR=1.61, 1.04-2.47, p=0.03). In PWOH, we found no significant association (aHR=1.27, 0.63-2.59, p=0.50), although the interaction was not significant (p= 0.49). Higher log (CAC+1) was also associated with all-cause mortality among all participants (aHR=1.37 per SD, 1.15-1.63, p<0.001) and among strata (PLWH, aHR=1.40, 1.13-1.73, p=0.002; and PWOH aHR=1.38, 1.00-1.91, p=0.049). Conclusion: CAC predicts all-cause mortality in a large cohort of PLWH and PWOH, with no significant difference in this association by HIV serostatus.