BACKGROUND AND AIMS: Colorectal serrated lesions (SLs) are precursors of colorectal carcinoma via the serrated neoplasia pathway. However, the success rate of endoscopic resection of large SLs is low. Therefore, this study aimed to determine the safety and efficacy of underwater EMR (UEMR) for SLs sized 10 to 20 mm. METHODS: This 2-center, prospective, observational study included patients with at least 1 SL sized 10 to 20 mm. We resected the SLs by UEMR and performed tattooing at the resection site. Surveillance colonoscopy was performed 12 months postoperatively to evaluate local recurrence. The primary outcome was the complete resection rate of UEMR, which was defined as en bloc resection with no serrated tissue in the 4 marginal biopsy samples and histologically negative margins. RESULTS: UEMR was performed for 65 SLs in 58 patients, with a median lesion size of 14 mm. The en bloc, R0 resection, and complete resection rates were 87.7% (57 of 65), 61.5% (40 of 65), and 60.0% (39 of 65), respectively. Adverse events included 1 (1.5%) immediate bleeding and 1 (1.5%) delayed perforation. Surveillance colonoscopy was performed in 50 patients with 57 scars, and the rates of identification for tattoos and scars were 94.7% (54 of 57) and 100% (57 of 57), respectively. The recurrence rate was 5.3% (3 of 57), and all 3 recurrent lesions were completely resected endoscopically. CONCLUSIONS: This 2-center prospective study demonstrated that UEMR for SLs sized 10 to 20 mm was comparable to previous conventional EMR outcomes.