OBJECTIVES Adjuvant therapy for patients with surgically resected GIST leads to a significant reduction in recurrence. The purpose of this study was to evaluate costs and outcomes associated with surgically resected localized GIST (SRLG) and recurrent GIST. METHODS We conducted a retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, containing information from the SEER cancer registry linked to administrative claims from Medicare. Patients with a diagnosis of GIST from 1993-2002 were identified using a combination of primary cancer site and ICD-O-2 histology codes typical for GIST, and the ICD-O-3 GIST code, where available. Patients with SRLG were retained and their Medicare claims scanned from the time of GIST diagnosis through 2005 to assess survival and health-care costs. All GIST patients were age and sex matched 1:1 to GIST free controls; patients with recurrence were matched to recurrence-free controls for recurrence analyses. GIST- and recurrence-attributable costs were estimated using the Kaplan-Meier Sample Average method using up to 10-years of follow-up data and computing the difference between cases and controls. RESULTS We identified 292 patients in the SEER-Medicare data with SRLG; 35 with recurrence. Median overall survival was 59 months among all GIST patients, and recurrence-free survival was 45 months. Median post-recurrence survival was 46 months. Recurrence-free survival was 82%, 69%, and 39% at 1, 2, and 5 years respectively. Per-patient costs ($2005 US) attributable to SRLG were ~$19,500 (95% CI $3,700, $37,500) with the majority of costs incurred in the first 3 years after diagnosis; the associated annual burden was estimated to be ~$33.1 million among ~4,100 prevalent cases. Per-patient costs attributable to GIST recurrence were ~$97,900 (95% CI $28,200, $197,500). CONCLUSIONS GIST recurrence is associated with poor survival and increased medical-care costs. Adjuvant treatments that delay or eliminate recurrence could substantially reduce the burden of GIST.