OBJECTIVE:: The purpose of this study was to determine whether the operative approach independently influenced recurrence and to identify perioperative predictors of recurrence. BACKGROUND:: Intraoperative parathyroid hormone (IoPTH) monitoring has enabled surgeons to perform minimally invasive parathyroidectomy (MIP). Yet, the long-term durability of this approach has recently been questioned. STUDY DESIGN:: A retrospective review was performed, and cases of initial neck surgery for nonfamilial primary hyperparathyroidism were selected for analysis. Cases were classified as either open parathyroidectomy (OP) when both sides of the neck were explored or MIP when only one side was explored. Kaplan-Meier estimates were plotted for disease-free survival, and a Cox proportional hazards model was developed to evaluate factors associated with recurrence for both the entire cohort and the MIP subset. Further comparisons were made between those who recurred and those who did not recur. RESULTS:: In the past 10-year period, 1368 parathyroid operations for primary hyperparathyroidism were performed at our institution. A total of 1006 were MIP whereas 380 were OP. There were no differences in recurrence between the MIP and OP groups (2.5% vs 2.1%; P = 0.68), and the operative approach (MIP vs OP) did not independently predict recurrent disease in our multivariate analysis. The percentage decrease in IoPTH was protective against recurrence for both the entire cohort (hazard ratio = 0.96; 95% confidence interval = 0.93-0.99; P = 0.03) and the MIP subset. A higher postoperative PTH also independently predicted disease recurrence. CONCLUSIONS:: Operative approach does not independently predict recurrent hyperparathyroidism. The percentage decrease in IoPTH is one of many adjuncts the surgeon can use to determine which patients are best served by bilateral exploration whereas the postoperative PTH can guide follow-up after parathyroidectomy. © 2013 Lippincott Williams and Wilkins.