Recent advances in preoperative imaging techniques and intraoperative parathyroid hormone (ioPTH) assays have made single-gland, minimally invasive parathyroidectomy (MIP) the preferred treatment option for most patients with primary hyperparathyroidism (pHPT). Despite this evolution, a recommendation for bilateral neck exploration (BNE) with four-gland dissection in all patients has recently been advocated by a parathyroid surgical group. The current study compares the long-term outcomes of MIP with those of conventional BNE with four-gland dissection in patients with pHPT.In order to objectively assess a recommendation in the literature that universal BNE with four-gland dissection is advisable, all patients undergoing an initial MIP with ioPTH assessment for pHPT in a tertiary endocrine practice during a 10-year period were reviewed. The cure rates from this procedure were compared with published results of conventional BNE with four-gland dissection.Of the 561 patients undergoing parathyroidectomy during the study period, 337 had initial surgery for pHPT; 282 of these patients met inclusion criteria and 212 had sufficient follow-up data available. A single adenoma was identified in 87.3% of cases. Preoperative imaging studies were co-localizing in 148 (69.8%), and 127 (85.8%) of these patients with co-localizing imaging required only single-gland surgery. Imaging studies did not co-localize in 49 patients, yet 32 (65.3%) of these patients were still cured with unilateral surgery. The cure rate for patients undergoing MIP was 98.6%, with a long-term recurrence rate of <2%.When coupled with the ioPTH assay, patients with at least one preoperative localizing study can undergo MIP and anticipate a cure rate of 99%, which is as good as or better than the published rates for conventional BNE with four-gland dissection. With unilateral surgery, the risks of permanent hypoparathyroidism and airway obstruction from bilateral vocal fold paralysis are completely eliminated. Therefore, despite recommendations to the contrary, most patients with pHPT should not have a planned four-gland exploration.III or IV.