OBJECTIVES: Since approval of imatinib, systemic therapy (ST) for gastrointestinal stromal tumors (GIST) has changed considerably. This study evaluated treatment patterns and costs across 3 large retrospective databases among GIST patients receiving imatinib.  METHODS: A retrospective study spanning July 2004-December 2011 analyzed data from 3 large integrated claims databases. Patients with a GIST-related ICD-9-CM code (151.0-154.0, 158.0, 159.0, 159.8, 159.9, 171.0, 171.4-171.9, 239.0) receiving imatinib were eligible if they (1) had a minimum eligibility of 6 months prior and 12 months following their first GIST diagnosis and (2) no previous diagnosis of cancer. Patients were divided into 2 cohorts: surgical (S) and non-surgical (NS). ST treatment patterns and corresponding GIST-related average monthly costs were evaluated.  RESULTS: There were 57 (24 S, 33 NS), 98 (62 S, 36 NS), and 276 (156 S, 120 NS) patients in each of the 3 databases meeting all inclusion criteria, respectively. Average monthly cost of first-line therapy ranged from $26,465 to $78,081, with variation being driven by length of treatment. 42%-56% of NS and 41%-58% of S patients received second-line therapy, costing an average of $3,197-$5,334 per month. The majority of patients in each database received imatinib mono- or combination therapy as second-line treatment (60%-74% NS; 74%-86% S). Third-line therapy was received by 13%-33% of NS and 19%-30% of S patients, with an average cost per month ranging from $2,354 to $30,993. Imatinib was also received third-line by the majority of the patients in 2 databases (59%-67% NS, 60-75% S); sunitinib was most commonly utilized (43% NS, 58% S) in the third database.  CONCLUSIONS: Over half of all patients receiving imatinib undergo surgery. Among both S and NS patients, second-line therapy for GIST was dominated by imatinib, while third-line therapy was dominated by imatinib or sunitinib.