Background: TNT has recently emerged as a standard treatment for LARC. However, use and outcome of the different TNT regimens in real-world practice are largely unknown. Methods: This is an international, multicentre, retrospective study sponsored by the Institut Jules Bordet, Brussels. Eligibility was limited to newly diagnosed LARC patients treated with TNT between March 2013 and May 2023 and outside the context of a clinical trial. The primary objective was to describe real-word practice across international centres. Secondary objectives included treatment safety and efficacy. Data were collected into a central electronic database, and remotely monitored. Descriptive statistics were used, and survival outcomes were estimated with Kaplan-Meier curves. Results: 1,272 eligible patients were included from 47 centres across four continents (Europe, Asia, North America and South America). Baseline characteristics were as follows: 63% males, median age 60 years (range 21-88), 47% low rectum, 26% cT4, 47% cN2, 49% EMVI+, 59% CRM+. In the overall population, 21% of the resected patients had a pathological complete response (pCR), while 11.3% were managed according to a watch-&-wait (w&w) strategy. Median follow-up was 24.1 months (IQR 23.7). Local and distant recurrences after curative-intent surgery occurred in 5.5% and 16.2% of patients, respectively. 3-year event-free survival (EFS) was 68.3%, while 3-year overall survival (OS) was 89%. Serious adverse events were reported in 4.3% of patients during radiotherapy, and in 14.7% during chemotherapy. Patient distribution according to the TNT sequence/regimen, and respective efficacy outcomes are reported in the table. Conclusions: This is the largest real-world study of TNT for LARC. Our findings show substantial variation in the choice of TNT sequence and regimen. Efficacy and safety results are overall in line with those reported in clinical trials, and confirm feasibility of TNT in a real-world setting. Patient recruitment is ongoing, and updated results with propensity score matching analyses will be reported at the meeting.