Background Five percent of gastrointestinal stromal tumors (GISTs) are primarily localized in the rectum. We analyzed the outcome of multimodality treatment for rectal GIST in a multicenter retrospective series. Methods All surgically treated patients with a rectal GIST were identified from four specialized centers in the Netherlands. Primary endpoints were disease-free survival (DFS) and overall survival (OS). Results Thirty-two patients (22 men and 10 women) with rectal GISTs were identified. Twenty-two patients received imatinib before surgery for a median of 9 (range 253) months (Group 1). Ten patients received no imatinib because of small tumor size or lack of availability (Group 2). Median tumor size before treatment was 9.3 (range 617) cm in Group 1 and median 6 (range 414) cm in Group 2. A complete resection was possible in 17/22 (77%) patients in Group 1 versus 7/10 (70%) in Group 2. Median DFS was not reached in Group 1, while it was 36 months in Group 2. Median OS was not reached in both groups. Conclusions Preoperative imatinib leads to downsizing of the tumors in Group 1. However, it has not led to less extensive surgery. The DFS is longer in patients treated with pre- and post-operative imatinib, without an effect on OS. J. Surg. Oncol. 2013;107:320323. (c) 2012 Wiley Periodicals, Inc.