OBJECTIVE To investigate the efficacy of transanal endoscopic microsurgery (TEM) combined with imatinib for rectal gastrointestinal stromal tumors(GIST). METHODS Clinical data of 35 patients with rectal GIST undergoing TEM at Peking Union Medical College Hospital from February 2008 to May 2017 were analyzed retrospectively. Operation details, postoperative recovery condition, and follow-up information were reviewed. The differences in clinicopathological features and perioperative parameters were compared between patients who received neoadjuvant therapy (12 patients, imatinib mesylate, oral, 400 mg daily for 6 months before surgery) and those without neoadjuvant therapy (23 patients). RESULTS Of 35 patients, 18 were males and 17 were females with the mean age of (49.3±13.3) years. Mean tumor diameter was (1.8±1.1) cm and mean distance from lower tumor margin to anal verge was (4.0±1.8) cm. Mean operative time was (82.4±21.1) minutes and mean blood loss was (11.7±7.5) ml. No conversion to laparotomy occurred. Complete resection with negative margins was achieved in all cases. Complications were classified according to Clavien-Dindo system: 4 cases of grade I, 3 of grade II and 1 of grade IIIb. The tumor size in patients who received neoadjuvant therapy reduced from (3.1±1.2) cm to (2.6±1.2) cm, though it was still larger than the tumor size in patients without neoadjuvant therapy[(1.5±0.8) cm, P<0.01]. No significant difference in operative time was found between patients with and without neoadjuvant therapy [(76.7±24.8) minutes vs. (85.4±18.8) minutes, P>0.05]. Thirty patients (85.7%) were followed up for (50.3±36.6) months, and no local recurrence or metastasis was observed. CONCLUSIONS TEM is safe and effective in the treatment of rectal GIST. Preoperative neoadjuvant therapy is beneficial to TEM in treating larger tumors without increasing operating time. Satisfactory follow-up result is observed.