Objective: To investigate the clinical characteristics, diagnosis and treatment methods of duodenal gastrointestinal stromal tumors (GIST). Methods: Data of 29 patients with pathologically proven duodenal GIST undergoing surgery from May 2000 to April 2012 were collected. The onset of the disease, clinical manifestations, imageological findings, treatment methods, pathological results and prognosis of these patients were retrospectively analyzed. Results: Of the patients, 14 were male and 15 were female with an average age of 51.95 years. The lesions were located in the bulb (2 cases), descending part (16 cases), horizontal part (8 cases), and ascending part (3 cases) of the duodenum, respectively. The initial symptoms were melena in 15 cases, hematemesis combined with melena in 2 cases, bloating and pain in upper abdomen in 7 cases, and general fatigue in 2 cases, while 3 cases demonstrated no overt symptoms. The tumor size ranged from 1.5 to 15.5 cm with an average of 6.9 cm, which was 1.5-5.0 cm in 19 cases, 5.0-10.0 cm in 7 cases, and >10 cm in 3 cases. The preoperative examinations comprised CT scan and/or MRI, gastroduodenoscopy, upper gastrointestinal contrast, and endoscopic ultrasonography. All patients underwent surgical treatment that included pancreaticoduodenectomy in 7 cases, segmental duodenal resection in 10 cases, local duodenal resection in 10 cases, and duodenal bulb plus gastric antral resection in 10 cases; 10 patients were treated with imatinib after surgery. According to Fletcher's risk classification, tumors in 2 cases were very low risk, in 11 cases were low risk, in 9 cases were intermediate risk, and 7 cases were high risk. Immunohistochemical results showed tumors in 23 cases were CD34 positive and in 27 cases were CD117 positive. Follow-up in 27 patients was obtained for 12 to 156 months, with an average of 54 months. Recurrence occurred in 5 patients, of whom 2 cases developed liver metastases and 3 had local recurrence. Two of the recurrent cases received no further treatment and died 30 months and 42 months later, respectively. Conclusion: Radical resection is effective treatment for duodenal GIST. The procedure used depends on the the size and location of the tumor. Better results can be expected under the premise of a negative surgical margin.