ObjectiveTo investigate the clinical characteristics and treatment of primary mediastinal yolk sac tumor (PMYST). MethodsWe collected the clinical data of PMYST patients who were admitted to the Department of Thoracic Surgery of Peking Union Medical College Hospital from September 2000 to September 2020. The clinical and pathological characteristics, treatment and prognosis of PMYST patients were retrospectively analyzed. Results Finally 18 patients were enrolled, including 17 males and 1 female with a median age of 22.0 (16.6, 26.2) years. Patients had increased level of alpha fetoprotein (AFP). The pathological type can be single yolk sac tumor or combined with other mediastinal germ cell tumors. Chemotherapy and radical surgery were the main treatment methods. Extensive resection was feasible for patients with tumor invasion of other organs. Seven patients developed lung or pleural metastasis after operation, and 3 of them had extrapleural metastasis. One patient recurred within 1 year after surgery. All patients were followed up by telephone or outpatient department. At the last follow-up, 5 patients survived, 9 died, and 4 were lost to follow up, with a median survival of 16.8 months. The median disease-free survival was 14.9 months. The survival rates at 1, 3 and 5 years were 73.3%, 28.6% and 11.8%, respectively. ConclusionPMYST often occurs in young-middle aged male patients. Preoperative puncture can provide an effective diagnostic basis. R0 resection, AFP returning to normal after treatment and no metastasis may be potential indicators of good prognosis. The overall prognosis of PMYST is poor, and some patients can achieve long-term survival after treatment.