Objective To study the effects and adverse reaction of imatinib mesylate used to prevent the recurrence of gastrointestinal stromal tumor (GIST) after resection. Methods 22 patients with primary gastrointestinal stromal tumor were included in the First Affiliated Hospital of Chongqing Medical University from January, 2007 to November, 2009 who received resection and were imageologically diagnosed as no residual tumor by enhanced CT or enhanced MRI after resection. They were all given imatinib mesylate 400 mg for oral use daily after resection (median-risk GIST: more than 1 year; high-risk GIST: more than 2 years). Patients’ 1-year and 2-year relapse-free survival (RFS) and adverse reaction were recorded during follow-up. Results Among 22 patients, there were 13 males and 9 females, with median age of 57.4 years, and 9 high-risk cases were included. The median follow-up lasted 34 months (24 to 48 months). Patients’ 1-year and 2-year RFS was 100% and 94.5%, respectively. Adverse reaction mainly included edema, nausea, abdominal pain, muscle or bone pain, thrombocytopenia, weakness, skin rashes, etc., most of which were mild or moderate and could be alleviated after treating symptoms. Conclusion Imatinib mesylate therapy given after resection is a safe and reliable method which could prolong RFS and prevent or delay the recurrence of GIST. However, further high-quality randomized controlled trial was required to verify its curative effects, since no control group has been set in our study.