Objective To evaluate the endoscopic therapeutic effect on Barrett esophagus (BE) with special intestinal metaplasia. Methods A retrospective analysis was performed on data of 56 patients of BE with special intestinal metaplasia who were diagnosed in Renmin Hospital of Wuhan University from January 2017 to December 2019 and treated with endoscopic radiofrequency ablation (ERFA) or endoscopic mucosal resection (EMR). The postoperative bleeding rate, feeding obstruction rate, operative time, hospital stay and residual or recurrent intestinal metaplasia lesions were studied. Results There were no significant differences between the ERFA group (n=43) and the EMR group (n=13) in terms of age, gender, length of BE, preoperative gastrointestinal symptoms and comorbidity (P>0.05). The postoperative bleeding rate [23.1% (3/13) VS 0, P=0.010] and feeding obstruction rate [30.8% (4/13) VS 4.7% (2/43), P=0.022] were higher in the EMR group compared with those in the ERFA group, and the operative time [6.0 (5.6, 6.2) min VS 5.4 (5.2, 5.5) min, Z=4.95, P<0.001] and hospital stay [6.0 (5, 7) d VS 3.5 (3, 4) d, Z=5.76, P<0.001] were longer in the EMR group. There were no significant differences in the incidences of postoperative pain or fever between the two groups (P>0.05). No residual or recurrent intestinal metaplasia lesions were observed during the follow-up in any EMR patient, and follow-up biopsies after the first treatment in the ERFA group revealed residual intestinal metaplasia lesions in 41.9% (18/43) patients, with a significant difference (P=0.005). Conclusion EMR is more thorough in the treatment of BE with special intestinal metaplasia, while ERFA is more widely used in clinical practice for simpler operation, shorter operative time, and less postoperative complications.