Purpose The standard treatment of rectal adenocarcinoma is total mesorectal excision (TME), in many cases requires a temporary or permanent stoma. TME is associated with high morbidity and genitourinary alterations. Transanal endoscopic microsurgery (TEM) allows access to tumors up to 20 cm from the anal verge, achieves minimal postoperative morbidity and mortality rates, and does not require an ostomy. The treatment of T2, N0, and M0 cancers remains controversial. Preoperative chemoradiotherapy (CRT) in association with TEM reduces local recurrence and increases survival. The TAU-TEM study aims to demonstrate the non-inferiority of the oncological outcomes and the improvement in morbidity and quality of life achieved with TEM compared with TME. Methods Prospective, multicenter, randomized controlled non-inferiority trial includes patients with rectal adenocarcinoma less than 10 cm from the anal verge and up to 4 cm in size, staged as T2 or T3-superficial N0-M0. Patients will be randomized to two areas: CRT plus TEM or radical surgery (TME). Postoperative morbidity and mortality will be recorded and patients will complete the quality of life questionnaires before the start of treatment, after CRT in the CRT/TEM arm, and 6 months after surgery in both arms. The estimated sample size for the study is 173 patients. Patients will attend follow-up controls for local and systemic relapse. Conclusions This study aims to demonstrate the preservation of the rectum after preoperative CRT and TEM in rectal cancer stages T2–3s, N0, M0 and to determine the ability of this strategy to avoid the need for radical surgery (TME). Trial registration ClinicalTrials.gov identifier: NCT01308190. Número de registro del Comité de Etica e Investigación Clínica (CEIC) del Hospital universitario Parc Taulí: TAU-TEM-2009-01.