Multiple sclerosis (MS) has been associated with reduced bone mineral density (BMD). The purpose of this study was to determine the possible factors affecting BMD in patients with MS. We included consecutive 155 patients with MS and 90 age-and sex-matched control subjects. Patients with MS exhibited significantly lower T-scores and Z-scores in the femoral neck and trochanter compared to the controls. Ninety-four (61%) patients had reduced bone mass in either the lumbar spine or the femoral neck; of these, 64 (41.3%) had osteopenia and 30 (19.4%) had osteoporosis. The main factors affecting BMD were disability, duration of MS, and smoking. There was a negative relationship between femoral BMD and EDSS and disease duration. No association with lumbar BMD was determined. There were no correlations between BMD at any anatomic region and cumulative corticosteroid dose. BMD is significantly lower in patients with MS than in healthy controls. Reduced BMD in MS is mainly associated with disability and duration of the disease. Short courses of high dose steroid therapy did not result in an obvious negative impact on BMD in the lumbar spine and femoral neck in patients with MS.