OBJECTIVES: With the approval of imatinib (ima), systemic therapy (ST) for gastrointestinal stromal tumors (GIST) has changed substantially. This study evaluated treatment patterns and costs of patients receiving first-line (1LT) ima for GIST. METHODS: A retrospective study spanning 1/1/03-9/30/11 was conducted utilizing pharmacy/medical claims data from a large health plan. Patients with GIST-related ICD9 codes who initiated ima were eligible. Patients were excluded if they received any chemotherapy prior to date of first diagnosis or ima. Adjuvant patients (APs) were defined as receiving GIST-related surgery prior to ima. Patients were followed from diagnosis to end of the study period or loss of continuous eligibility to describe post-ima ST and evaluate corresponding GIST-related average monthly costs.  RESULTS: One hundred patients (45 APs) with average follow-up time of 1113 days (range 385–2,901 days) met all inclusion criteria. The average time between first diagnosis and initiation of ima therapy was 207 days for AP versus 140 days for non-adjuvant patients (NAPs). Average monthly costs prior to ima therapy were $7,025; APs, $11,095/month. APs remained on ima therapy for an average of 463 days versus 404 days for NAPs. Monthly therapy costs across both cohorts were $3919 (SD=$1822), almost 92% of total monthly costs. Twenty-one patients moved onto post-ima second-line therapy (2LT), with 81% (n=17) receiving sunitinib (sun). APs moving onto second-line therapy remained on treatment 148 days versus 256 days for NAPs. 2LT average monthly cost: AP=$8813; NAP=$5894; over 70% related to ST. 6 of the 21 patients received third-line therapy (3LT) (3-nilotinib, 2-sorafenib, 1-cyclophosphamide) for an average of 48 days; treatment costs averaged $1774/month. CONCLUSIONS: Post-ima 2LT for GIST was dominated by sun, while 3LT varied among the few patients who initiated this line of care. Across all lines of care, therapy cost was the primary driver of cost.