Objective. The study was aimed to assess the effect of hydrocortisone (HC) replacement therapy on bone mineral density (BMD) and bone turnover markers in patients with primary adrenal insufficiency (PAI). Methods. A cross-sectional study was conducted in 37 PAI patients treated with HC. BMD and selected bone turnover markers (β-crosslaps and osteocalcin) were measured. A stepwise binary logistic regression model was applied to determine the independent variables associated with low BMD. Results. Osteoporosis was noted in 14.3% and osteopenia in 34.3% of cases. These patients were older (p=0.01) and received higher daily HC dose compared to patients with normal BMD (p=0.01). BMD values in the lumbar spine and the femoral neck were negatively correlated with daily HC dose (r=–0.36, p=0.03 and r=–0.34, p=0.05, respectively). Plasma osteocalcin was negatively correlated with disease duration (r=–0.38, p=0.02) and cumulative HC dose (r=–0.43, p<0.01). In multivariate analysis, a daily HC dose ≥12 mg/m2/day was independently associated with a higher risk of osteopenia/osteoporosis [OR (95% CI), 9.0 (1.1–74.6); p=0.04]. Conclusions. Impaired bone mineralization in patients with PAI is correlated with HC dose. A daily HC dose ≥12 mg/m2/day was associated with an increased risk of osteopenia and osteoporosis in these patients.