PURPOSE: To identify an optimal postoperative day 3 (POD3) C-reactive protein (CRP) cut-off for predicting major complications in colorectal cancer (CRC) patients. Secondary objectives included identifying patient and surgical factors associated with POD3 CRP levels and assessing the accuracy of the cut-off across subgroups. METHODS: A retrospective cohort study of 1536 CRC patients who underwent an oncological resection was conducted. The predictive accuracy of POD3 CRP for major complications was tested using Receiver Operating Characteristics curves. The CRP cut-off was tested across subgroups. Multivariable logistic regression analyses was performed to evaluate the predictive value of the POD3 CRP cut-off, while also determining whether patient and surgical characteristics independently predicted major complications. RESULTS: An optimal cut-off of 114 mg/L was identified, with a sensitivity of 0.80 and specificity of 0.59 and an Area Under the Curve for POD3 CRP of 0.78. Sensitivity remained consistently high across all subgroups, whereas specificity exhibited variability, with a notable decrease observed in the subgroups
aged 66-69, obese, ASA III and open surgery. After adjusting for patient and surgery characteristics, a POD3 CRP level above 114 mg/L was associated with a significant 5.29-fold increase in the odds for developing major complications. CONCLUSIONS: A POD3 CRP cut-off of 114 mg/L is an effective predictor of major complications following CRC surgery, supporting safe early discharge. The cut-off remains a reliable predictor, even after adjusting for patient and surgery factors.