We tested whether the association between bone mineral density (BMD) and coronary artery calcification (CAC) varies according to dyslipidemia in community-living individuals. Between 2002 and 2005, 305 women and 631 men (mean age of 64 years), who were not taking lipid-lowering medications or estrogen were assessed for spine BMD, CAC, and total (TC), HDL- and LDL-cholesterol and triglycerides. Participants were a random sample from the Multi-Ethnic Study of Atherosclerosis (MESA) without clinical cardiovascular disease. Spine BMD at the L3 vertebrate was performed by computer tomography (CT). CAC prevalence was measured by CT. The total cholesterol to HDL ratio (TC:HDL) ≥ 5.0 was used as the primary marker of hyperlipidemia. The association of BMD with CAC differed in women with TC:HDL < 5.0 versus higher (p-interaction = 0.01). In age- and race-adjusted models, among women with TC:HDL < 5.0, each SD (43.4 mg/cc) greater BMD was associated with a 25% lower prevalence of CAC (prevalence ratio [PR] 0.75, 95% confidence interval [CI] 0.63-0.89), whereas among women with higher TC:HDL, higher BMD was not significantly associated with CAC (PR 1.22, 95% CI 0.82-1.82). Results were similar using other definitions of hyperlipidemia. In contrast, no consistent association was observed between BMD and CAC in men, irrespective of the TC:HDL ratio (p interaction 0.54). The inverse association of BMD with CAC is stronger in women without dyslipidemia. These data argue against the hypothesis that dyslipidemia is the key factor responsible for the inverse association of BMD with atherosclerosis.