BackgroundSerum C-reactive protein (CRP) is commonly used by surgeons to raise suspicion of anastomotic leakage and other infectious complications, but most studies on optimal cut-off values are retrospective with a small sample of patients. The aim of this study was to determine the accuracy and optimal cut-off value of CRP for anastomotic leakage in patients following esophagectomy for cancer.Materials and methodsConsecutive minimally invasive esophagectomy for esophageal cancer patients was included in this prospective study. Anastomotic leakage was confirmed if a defect or leakage of oral contrast was seen on a CT scan, by endoscopy or if saliva was draining from the neck incision. Diagnostic accuracy of CRP was assessed by receiver operator curve (ROC) analysis. Youden’s index was adopted to determine the cut-off value.ResultsA total of 200 patients were included between 2016 and 2018. Postoperative day 5 showed the highest area under the ROC (0.825) and optimal cut-off value of 120 mg/L. This resulted in a sensitivity of 75%, specificity of 82%, negative predicting value of 97%, and positive predicting value of 32%.ConclusionsCRP on postoperative day 5 can be used as a negative predictor for and can be used as a marker to raise suspicion of anastomotic leakage following esophagectomy for esophageal cancer. When CRP exceeds 120 mg/L on postoperative day 5, additional investigations should be considered.