Objective: To determine whether surgical volume influences the cause of operative failures after parathyroidectomy for hyperparathyroidism. Summary and Background Data: The surgical success rate for hyperparathyroidism from high-volume centers exceeds 95%, but some patients have unsuccessful parathyroidectomies. Although operative failure can be due to hyperfunctioning parathyroid glands in ectopic locations, less experienced surgeons may be more likely to miss an abnormal parathyroid in normal anatomic locations, which we describe as "preventable operative failure." Methods: We used 2 prospective databases containing over 2000 consecutive patients who underwent parathyroidectomy. We identified 159 patients with persistent/recurrent hyperparathyroidism subsequently cured with additional surgery. The initially failed operations were classified as being performed at high- (>50 cases/yr) or low-volume (<50 cases/yr) hospitals. Hospital volume was obtained from a Wisconsin state database of 89 hospitals, which reported 6336 parathyroid operations during the same decade. Results: Patients who initially failed their operation performed at the high- or low-volume centers were similar with regard to age, laboratory values, gender, and parathyroid weights. Despite a higher incidence of multigland disease (which increases the likelihood of operative failure) in the high-volume group, patients in the low-volume group were more likely to have a missed parathyroid gland in a normal anatomic location (89% vs. 13%, P < 0.0001), and thus a higher proportion of preventable operative failures. Conclusions: Surgical volume influences the failure pattern after parathyroidectomy for hyperparathyroidism. Preventable operative failures are more common in low-volume centers. Copyright © 2010 by Lippincott Williams & Wilkins.