We reviewed our experience with ectopic mediastinal parathyroidectomy. Between March 1980 and September 2010,mediastinal parathyroidectomy was performed in33 patients with hypercalcemia secondary to hyperparathyroidism. Primary hyperparathyroidism was the main diagnosis in 32 patients (97%). Technetium-sestamibi scan was used in 23 (70%) for preoperative localization. Minimally invasive resections were performed in 18 patients (55%), and 15 (45%) underwent open surgery. The most common minimally invasive surgery approach was video-assisted thoracoscopy in 9 patients (27%); the most common open approach was median sternotomy in 11 (33%). Intraoperative parathyroid hormone monitoring was used in 22 patients (67%). The ectopic glands were intrathymic in 15 patients (45%), in the aortopulmonary window in 7 (21%), and in other intrathoracic locations in the remaining 11 (33%). Parathyroid adenomas were identified in 21 patients (64%); parathyroid hyperplasia and carcinoma were identified in 9 (27%) and 3 (9%), respectively. No early mortality occurred in either group. Reoperation was required in 1 patient in the minimally invasive surgery group because of hemothorax. Morbidity occurred in 8 patients (24%), the most common of which was hypocalcemia in 4 (12%). The mean length of stay was significantly shorter in the minimally invasive surgery group (2 versus 6 days; p < 0.001) but mortality and morbidity were not statistically different between the two groups (p= 0.05). Mean follow-up was 3 ± 3.7 years. Minimally invasive mediastinal parathyroidectomy has similar outcomes to open surgery, with significantly shorter length of hospital stay.