HIV-infected individuals suffer from accelerated aging, which manifests as premature cardiovascular and bone disease. However, little is known of the association of these two disorders in the HIV population. Our objective was to investigate the association between a marker of atherosclerosis (coronary artery calcium [CAC]) and low bone mineral density (BMD) in a cross-sectional cohort of HIV-infected patients. The study was conducted at the University of Modena and Reggio Emilia, Italy. A total of 636 consecutive middle-aged, HIV-infected subjects were recruited between January 2006 and December 2010. All patients underwent CAC and BMD assessment. Patients were categorized according to a CAC score <100 or >100 units based on previous literature that identified this cut-point as a marker of increased risk. Low femoral and lumbar spine BMD was defined as <25th percentile value for the study cohort. Logistic regression and bootstrap analysis were used to assess the independent association between CAC and BMD. The main outcome measure was a CAC score >100. Patients with CAC > 100 were older and more likely to be men, diabetic, and overweight. Patients with CAC < 100 had better renal function and a lower cardiovascular risk profile. After adjusting for age, sex, traditional and HIV-specific risk factors, vitamin D level, and PTH level, there was a significant association between CAC > 100 and low BMD for the femur (OR = 2.33, 95 % CI 1.09-4.99; p = 0.02) but not for the spine. Bootstrap analyses confirmed these findings. In summary, CAC was independently associated with low femoral BMD in HIV-infected patients. Future studies should test whether therapies that attenuate cardiovascular risk in HIV favorably impact bone health.