Background: The standard treatment of locally advanced rectal cancer (LARC defined as T3-T4, N+) consists of giving chemoradiation therapy (CT/RT) followed by total mesorectal excision (TME) after 6-8 weeks followed by chemotherapy (CT) adjuvant. Recently, total neoadjuvant therapy (TNT) has shown greater efficacy in terms of increasing the rate of complete pathological response (pCR) and reducing local and systemic relapse, in addition to increasing sphincter preservation. The objective of this study was to know the percentage of pCR (ypT0N0) presented by Mexican patients with LARC treated at the National Cancer Institute (INCan) with the TNT (implemented in 2019) vs. standard treatment. Methods: An observational, analytical, and retrospective study was carried out, with a non-probabilistic sampling of patients with LARC treated at INCan from 2016 to 2021. Comparisons of continuous numerical variables for independent samples were analyzed using Student's t test or Mann-Whitney U test (depending on its distribution). To examine the association in the discrete variables, the X2 test or Fisher's exact test (according to the case) was used. The association between continuous variables was analyzed using Pearson's or Spearman's correlation coefficients according to the distribution. Statistical difference was considered significant when p < 0.05. The analysis was performed with the statistical package SPSS v26.0. Results: 286 patients were analyzed (N=76 corresponded to TNT), mean age was 57 years, 43% were female, 84% were stage III and 64% had a lower rectal tumor. Complete TME was present at 78.9%. The pCR rate was 45.16% with TNT vs. 22.39% with CT/RT (RR 0.70, 95% CI (0.56-0.90) p= 0.001). 18% recurrences and/or progressions were identified in the TNT group vs. standard treatment (28.2%) with a tendency to statistical significance (RR 0.6 95% CI (0.36-1.08) p= 0.08). 7% mortality was reported with TNT vs. 19% with standard therapy (RR of 1.15, CI 95% (1.05-1.26) p= 0.013). Conclusions: TNT was shown to increase the percentage of complete pathological responses compared to chemoradiotherapy treatment in real-world population attended at INCan. The follow-up of these patients is still short to know the final impact of TNT in terms of relapse-free survival and overall survival.