After elective colon cancer resection, POD2 CRP below 100 mg/L identified patients with about a 1% risk of major anastomotic leak—potentially supporting earlier discharge.

• In two cohorts, this threshold had a 98.8% and 99.0% negative predictive value; 46–60% of patients were below it.
• With CRP at or above 100 mg/L, leak rates were about 8%; a falling POD3/POD2 CRP ratio further identified a lower-risk group.

The two-step approach classified nearly 90% of patients for discharge by POD2 or 3 with leak risk near 1%. These results apply to major leaks in elective colon cancer surgery; CRP should support, not replace, clinical assessment.