The benefit of aspirin in cancer of the colon and rectum is already known. Recently, it was described its potential activity during chemoradiotherapy, with higher rate of tumor downstaging. Furthermore, induction chemotherapy followed by chemoradiation represents an attractive approach, with more favorable compliance and toxicity profiles. The aim of this study was to evaluate the efficacy of total neoadjuvant treatment and assess the efficacy and feasibility of aspirin use during chemoradiotherapy for high-risk rectal cancer.