To compare total mesorectal excision (TME) techniques combined with sphincter-sparing procedure in high-risk patients (HRPs). TME is the standard treatment for rectal cancer, but can be challenging in HRPs. The available surgical approaches must be compared, especially in HRPs. Prospective, observational, multicenter trial to compare laparotomy (OTME), laparoscopy (LTME), robotic-assisted surgery (RTME), and transanal surgery (TaTME) in HRPs. The composite primary outcome included circumferential radial margin (CRM) ≥1mm, TME grade II-III, and absence of Clavien-Dindo grade III-IV complications. Three propensity score analyses were performed (LTME vs. RTME, RTME vs. TaTME, LTME vs. TaTME). 1078 HRPs (75% of men, median body mass index of 27kg/m2, 50% of tumors in the lower third of the rectum) underwent surgery. The RTME and TaTME groups included patients with more advanced and lower tumors and coloanal anastomosis (P<0.001). Operative time was longer for RTME surgery (P<0.001). Conversion rate was similar for minimally invasive procedures (4.5%). The global R0 resection rate was 96% without difference among techniques. The primary outcome rates were 82.4%, 64.3%, 74.7%, and 80.3% for LTME, OTME, RTME, and TaTME, respectively. None achieved the expected success rate (85%), and propensity score analyses found no differences. Operative results were similar between high- and low-volume inclusion centers only for RTME. The RESET trial yielded high-quality results despite focusing on HRPs. Minimally invasive procedures showed similar sphincter-sparing procedure outcomes, but LTME included patients with more favorable tumors. Oncologic and functional outcomes will be evaluated at 2 years (ClinicalTrials.gov, ID: NCT03574493).