Background: Minimally invasive parathyroidectomy (MIP) under local/cervical block anesthesia (LA) is safe and effective for patients with primary hyperparathyroidism (HPT). Advantages of LA versus general anesthesia (GA) for these focused procedures have not been clearly demonstrated. Methods: Between 3/01 and 6/04, 177 consecutive patients with primary HPT and positive localization studies underwent MIP. Seventy-three (41%) had surgery under LA while 104 (59%) had GA. Primary endpoints were IV narcotic use, anti-emetic use, nausea, vomiting, and post-operative pain. Results: Patients who had parathyroidectomy under LA were older (64 ± 2 vs. 57 ± 2 years, P = 0.001). Cure and complication rates were identical between the two groups. Patients who had parathyroidectomy under LA required less IV narcotic pain mediation (mean morphine equivalents 11.4 ± 1.3 mg vs. 22.5 ± 1.1 mg; P < 0.001) compared to GA patients. The LA patients had better pain control as shown by lower post-operative peak pain scores (2.9 ± 0.3 vs. 5.0 ± 0.4; P < 0.001) and lower overall pain scores (mean 1.9 ± 0.2 vs. 3.1 ± 0.2; P < 0.001). The LA group required fewer anti-emetic medications compared to the GA patients (mean 0.4 ± 0.1 vs. 1.7 ± 0.1 doses; P < 0.001). Fewer LA patients experienced post-operative nausea (16% vs. 49%; P < 0.001), and vomiting (7% vs. 24%; P = 0.002). Length of stay was similar between the groups (0.4 ± 0 vs. 0.3 ± 0; P = 0.22). Conclusions: In this study the choice of anesthesia did not affect surgical cure rate, morbidity, or length of stay. LA was associated with significantly lower post-operative pain, nausea, and vomiting. LA appears to offer specific advantages more than GA for patients undergoing MIP. © 2006 Society of Surgical Oncology.