BACKGROUND: Prolonged postoperative ileus (PPOI) is a major complication in patients undergoing colorectal resection. The aim of this study was to analyze the risk factors contributing to PPOI, and to develop an effective nomogram to determine the risks of this population. METHODS: A total of 1,254 patients with colorectal cancer who underwent radical colorectal resection at Fujian Cancer Hospital from March 2016 to August 2021 were enrolled as a training cohort in this study. Univariate analysis and multivariate logistic regressions were performed to determine the correlation between PPOI and clinicopathological characteristics. A nomogram predicting the incidence of PPOI was constructed. The cohort of 153 patients from Fujian Provincial Hospital were enrolled as a validation cohort. Internal and external validations were used to evaluate the prediction ability by area under the receiver operating characteristic curve (AUC) and a calibration plot. RESULTS: In the training cohort, 128 patients (10.2%) had PPOI after colorectal resection. The independent predictive factors of PPOI were identified, and included gender, age, surgical approach and intraoperative fluid overload. The AUC of nomogram were 0.779 (95% CI: 0.736-0.822) and 0.791 (95%CI: 0.677-0.905) in the training and validation cohort, respectively. The two cohorts of calibration plots showed a good consistency between nomogram prediction and actual observation. CONCLUSIONS: A highly accurate nomogram was developed and validated in this study, which can be used to provide individual prediction of PPOI in patients after colorectal resection, and this predictive power can potentially assist surgeons to make the optimal treatment decisions.