OBJECTIVE: The aim of the study was to investigate the association between high-density lipoprotein (HDL) and bone status taking into account serum vitamin D levels in postmenopausal Iranian women. METHODS: During January 2015 and February 2016, a total of 488 postmenopausal Iranian women participated in this cross-sectional study, all of whom were not taking osteoporosis medication and were not suffering from any chronic disorder. Dual X-ray absorptiometry was used to assess bone mineral density (BMD) of the total hip, femoral neck, and lumbar vertebrae (L2-L4). Each person was categorized based on the World Health Organization osteoporosis criteria in at least one skeletal region. At the end of the data collection, lipid profiles and vitamin D levels were measured for all participants. Vitamin D serum levels less than 30 ng/mL were defined as vitamin D deficiency or insufficiency. RESULTS: 27.9% of all participants displayed osteoporosis. Osteoporotic participants tended to be older with higher HDL serum levels (P < 0.001). No significant difference was seen in low-density of lipoprotein, total triglyceride, and total cholesterol levels among participants (P > 0.05). In a univariate model, after adjusting for age, menopausal age, obesity, physical activity, and use of antihyperlipidemic drugs (statins), there were significant negative associations among HDL levels and BMD values and T-score in the three regions (P < 0.004). Interestingly, after classification of participants based on vitamin D levels and adjustment for confounding factors, these significant negative associations between HDL levels and BMD values as well as T-score were observed only in participants with vitamin D deficiency or insufficiency, in the three regions (P < 0.008). CONCLUSIONS: Our data show that in postmenopausal women with vitamin D deficiency, serum levels of HDL have negative correlation with bone status.