189 Background: The standard first-line treatment for unresectable metastasis or recurrence gastrointestinal stromal tumors (GIST) is imatinib mesylate(IM), a selective tyrosine kinase inhibitor. Although IM has markedly improved the prognosis of patients with advanced GIST, half of the patients experience tumor progression within two years because of resistance to IM. And IM-resistant GIST is basically treated by other kind of TKI, in addition, surgical treatment can be considered as one of treatment options. The aim of this study was to clarify the significance of surgical treatment for IM-resistant GIST in the era of second-line TKI treatment. Methods: We retrospectively analyzed consecutive 35 GIST patients who have developed IM-resistance between 2004 and 2015. We assessed clinicopathological characteristics, postoperative outcomes, imatinib-failure free survival(IFFS), and overall survival(OS) in patients who underwent surgical resection for the IM-resistant lesions. Results: The study enrolled 24 male patients and 11 female patients. The median [range] age was 61 [39-83] years. The primary sites were stomach / small intestine / duodenum: 16 / 14 / 5 cases and resection for primary sites was performed in 32 cases. The median [range] period of IM administration until resistance was 26 [2-119] months, and the resistant lesion sites were liver / peritoneum / primary lesion / local recurrence / bone: 17 / 18 / 2 / 1 / 1 cases (with duplication). Resection for resistant lesions was performed in 18 cases (51%), of which 13 cases (72%) underwent R0 / 1 resection. The postoperative complications ( > Clavien-Dindo classification Grade II) were observed in 3 patients: Biliary leakage, abdominal abscess, and diaphragmatic hernia. IM was resumed promptly after surgery in all 18 patients who underwent resection for IM-resistant lesions, and the median [range] period of IM administration was 22.2 [0.9-56] months. In 5 cases, multiple surgical treatments were performed and second-line TKI was administered in all except for two patients who have still been treated as IM. The median OS was 49 months. Conclusions: It was suggested that surgical treatment for IM-resistant GIST may be safe and effective for appropriate cases.