BACKGROUND AND AIM: Antiepileptic drugs are associated with bone loss and fractures. Data in children is scarce and the impact of new therapies and of low vitamin D is not clear. This study assessed predictors of bone mineral density (BMD) in 225 ambulatory patients with epilepsy. METHODS: BMD and detailed clinical information were obtained from 137 adults mean age of 31 years, on therapy for a mean of 11.7 years, and 88 children mean age of 13 years, on therapy for an average of 4.7 years. RESULTS: Hypovitaminosis D was common in epileptic patients. BMD was reduced in adults but not children with epilepsy, by 0.3-0.6 SD depending on the skeletal site measured, compared to controls. Duration of treatment, but not vitamin D levels, was negatively correlated with BMD at the hip in adults. Bone density was reduced with the use of both enzyme and non-enzyme-inducing drugs, with both mono- and polytherapy, and was most severely reduced at the spine and hip with the use of enzyme-inducing drugs. In the multivariate analyses, polytherapy in children and duration of therapy and enzyme-inducing drugs in adults were independent predictors of BMD. CONCLUSION: Antiepileptic drug therapy is associated with low bone density at clinically relevant skeletal sites, projecting into a possible doubling of fracture risk. Age, therapy duration, polypharmacy and the use of enzyme-inducing drugs were risk factors. Newer drugs may be associated with deleterious effects on bone. Skeletal monitoring with varying intervals, depending on the individual risk profile, is indicated.