Abstract： Objective To investigate the clinical effect of surgery following systemic targeted therapy of tyrosine kinase inhibitors (TKIs) in patients with metastatic gastrointestinal stromal tumors (GIST). Methods From June 2007 to December 2009, data of 15 consecutive patients with metastatic GIST treated with imatinib/sunitinib followed by surgery were retrospectively analyzed. Results Disease responses to TKI treatment was categorized into controlled disease (including partial response and stable disease)(6. 40.0%), limited progression(4, 26.7%), and generalized progression(5, 33.3%), respectively. Surgeries were performed after mean 12 months following TKI therapies. Gross complete resection or optimal debulking with minimal residual disease were managed to performed in 8/10 patients with disease controlled and limited progression, while optimal debulking only achieved in 2/5 patients with generalized progression. Surgical morbidity was 20.0% (3/15). After operation, patients with disease controlled and limited progression had a median progression-free survival of 25.0 months and 2-year overall survival rate of 100%. In contrast, for patients with generalized progression, the median progression- free survival was 3 months (P <0.01), and median overall survival 10.5 months. Conclusions Patients with metastatic GIST who have controlled disease or limited progression to TKI therapy can benefit from surgical resection. Surgery should be selective in patients with generalized progression since surgery hardly improves survival in these patients.