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Purpose: The aim of this study was to establish a validated nomogram to predict risk factors for major post-operative complications in patients with rectal cancer (RC) by analyzing the factors contributing to major post-operative complications in RC patients., Methods: We retrospectively collected baseline and surgical information on patients who underwent RC surgery between December 2012 and December 2022 at a single-center teaching hospital. The entire cohort was randomly divided into two subsets (60% of the data for development, 40% for validation). Independent risk factors for major post-operative complications were identified using multivariate logistic regression analyses, and predictive models were developed. Area under the curve (AUC) was calculated using receiver operating characteristic curve (ROC) to assess predictive probability, calibration curves were plotted to compare the predicted probability of the nomogram with the actual probability, and the clinical efficacy of the nomogram was assessed using decision curve analysis (DCA)., Results: Our study included 3151 patients who underwent radical surgery for RC, including 1892 in the development set and 1259 in the validation set. Forty (2.1%) patients in the development set and 26 (2.1%) patients in the validation set experienced major post-operative complications. Through multivariate logistic regression analysis, age (p<0.01, OR=1.044, 95% CI=1.016-1.074), pre-operative albumin (p<0.01, OR=0.913, 95% CI=0.866-0.964), and open surgery (p<0.01, OR=2.461, 95% CI=1.284-4.761) were identified as independent risk factors for major post-operative complications in RC, and a nomogram prediction model was established. The AUC of the ROC plot for the development set was 0.7161 (95% Cl=0.6397-0.7924), and the AUC of the ROC plot for the validation set was 0.7191 (95% CI=0.6182-0.8199). The predicted probabilities in the calibration curves were highly consistent with the actual probabilities, which indicated that the prediction model had good predictive ability. The DCA also confirmed the good clinical performance of the nomogram., Conclusion: In this study, a validated nomogram containing three predictors was created to identify risk factors for major complications after radical RC surgery. Due to its accuracy and convenience, it could contribute to personalized management of patients in the perioperative period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Yuan, Qu, Diao, Hai, Xiang and Peng.)