INTRODUCTION: Primary hyperparathyroidism (PHPT) results in increased bone turnover, resulting in bone mineral density (BMD) reduction and a predisposition towards fractures. Parathyroidectomy (PTX) is the only definitive cure. OBJECTIVE: The primary goals of this study were to investigate the impact of PTX on BMD in patients with PHPT and to identify factors associated with post-operative BMD improvement using a multivariate model. METHODS: Between 1999 and 2010, a total of 757 patients underwent PTX for treatment of PHPT; 123 patients had both a pre- and a post-operative dual-energy X-ray absorptiometry (DEXA) scan. A prospective database was queried to obtain information about patient demographics, medications, comorbidities, and pre- and post-operative laboratory values. A Cox regression model was used to stratify patients and to identify factors that independently predict BMD response following PTX in this patient population. RESULTS: Overall, mean percent change in BMD was +12.31 % at the spine, +8.9 % at the femoral neck (FN), and +8.5 % at the hip, with a mean follow-up of 2.3 ± 1.5 years. A total of 101 (82.1 %) patients had BMD improvement at their worst pre-operative site. In patients who improved, 69.9 % (n = 86) had >5 % increase. Factors associated with BMD improvement at the worst pre-operative site were as follows: male gender (hazard ratio [HR] 2.29; 95 % confidence interval [CI] 1.54-4.21); pre-operative BMD with T-score less than -2.0 (HR 1.89; 95 % CI 1.11-2.39); age <55 years (HR 1.74; 95 % CI 1.14-2.25); BMD DEXA scan at >2.5 years post-operatively (HR 1.71; 95 % CI 1.09-2.17); history of previous fracture (HR 1.24; 95 % CI 1.05-1.92); and private insurance (HR 1.18; 95 % CI 1.06-2.1). The use of bisphosphonates, estrogens, vitamin D supplementation, or tobacco; obesity; history of previous PTX, serum calcium or parathyroid hormone levels were not independently associated with post-operative BMD improvement. CONCLUSION: Osteoporosis is one of the established National Institutes of Health criteria for PTX in asymptomatic patients with PHPT, but BMD improvement is not consistently seen during the post-operative period. Gender, age, more severe pre-operative bone disease, and insurance status were all predictors for greater BMD improvement following PTX. Further studies with a rigorous post-operative BMD regimen are needed in order to validate these results.