INTRODUCTION: Endoscopic mucosal resection (EMR) of large (≥20 mm) lateral spreading lesions (LSLs) of the colon is effective in decreasing the incidence of colorectal malignancy and avoiding surgery. A drawback of colonic EMR is the adenoma residual/recurrence rate (15-30%) on first surveillance colonoscopy. A single randomized controlled trial (RCT) from Australia showed that prophylactic coagulation of the EMR margin with the tip of a snare (snare tip soft coagulation - STSC) reduced adenoma recurrence. Definitive evidence usually requires at least two RCTs that corroborate the findings. The aim of our study was to confirm the efficacy of STSC to reduce the rate of residual/recurrent adenoma following EMR. METHODS: An RCT comparing standard EMR (control arm) to EMR + STSC (active arm) for the resection of large LSLs at three tertiary referral centers (Mayo Clinic campuses in Jacksonville, FL; Scottsdale, AZ; and Rochester, MN) was performed. Surveillance colonoscopies with photo documentation using standardized near-focus NBI and biopsies were performed at 6 months post resection. The primary endpoint was the presence of residual/recurrent adenoma at the prior EMR site. The protocol was approved by the Institutional Review Board of Mayo Clinic and registered (NCT01789749). RESULTS: A total of 148 patients from the 3 sites (117, FL; 17, AZ; and 14, MN) were randomized: 75 in the control arm and 73 in the active arm. The primary outcome, histologically confirmed residual/recurrence at first follow-up, was available for 114 patients. Median duration to first follow-up was 6.7 months [IQR 6, 8.7]. Except for the variables of prior biopsy and adenoma recurrence, there were no differences between the two groups with regard to other variables, including patient demographics, size and location of lesions, polyp histology, and use of clips (Table 1). Among the 114 patients who had their first follow-up, 27 patients had histologically confirmed residual/recurrence: 20/58 (34%) in the control arm versus 7/56 (12%) in the active arm, unadjusted RR = 0.36 (95% CI 0.17–0.79, P = 0.011) (Table 2). When adjusting for previous biopsy, the use of STSC was associated with a lower rate of residual/recurrent adenoma with adjusted RR = 0.37 (95% CI 0.17–0.83; P = 0.015). CONCLUSION: The use of snare tip soft coagulation as adjuvant treatment to EMR of large lateral spreading lesions significantly reduces the risk of residual or recurrent adenoma at follow-up.Table 1.: EMR versus EMR + STSC for Large Lateral Spreading LesionsTable 2.: Adenoma residual/recurrence among patients who had a first follow-up colonoscopy