Purpose: To review our institutional surgical outcomes with primary mediastinal cysts (PMCs) and elucidate the clinicopathological differences among several histological PMC variants.Methods: We retrospectively reviewed 108 patients who underwent surgery for PMC at our institution between 1997 and 2012.Results: There were 54 thymic cysts (TCs), 26 bronchogenic cysts (BCs), 16 mature cystic teratomas (MCTs), 11 pericardial cysts (PCs), and 1 esophageal duplication cyst. Surgical approach was via thoracoscopy in 44, thoracotomy in 24, median sternotomy in 39, and hemiclamshell incision in 1. Pathological complete resection was achieved in all patients. Postoperative complications occurred in 13 patients. There was no postoperative mortality. All patients were recurrence-free after a mean follow up of 41 ± 26 months. MCT was significantly associated with larger cyst size (p <0.001) more frequent combined resection of invaded organs (p <0.001), more intraoperative bleeding (p = 0.005), and longer duration of operation (p = 0.022) than the 3 other groups (TC, BC, and PC).Conclusion: Surgical treatment for PMC is safe and efficacious regardless of approach. Patients with MCT may require more aggressive surgeries than those with other histological variants, reflecting their potential for invasion into surrounding structures and larger cyst size.