Three-hundred-twenty-four (324) patients with stage II or III rectal adenocarcinoma were treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients then underwent total mesorectal excision (TME) or were assigned to a watch-and-wait status on the basis of tumor response. Three-year TME-free survival was 41% in the INCT-CRT group and 53% in the CRT-CNCT group. Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival.