BackgroundC-reactive protein is a useful biological tool to predict infectious complications, but its predictive value in detecting organ-specific surgical site infection after liver resection has never been studied. We aimed to evaluate the predictive value of c-reactive protein and determine the cut-off values to detect postoperative liver resection–surgical site infection. MethodsA multicentric analysis of consecutive patients with liver resection between 2018 and 2021 was performed. The predictive value of postoperative day 1, postoperative day 3, and postoperative day 5 C-reactive protein levels was evaluated using the area under the receiver operating characteristic curve. Cut-off values were determined using the Youden index in a 500-fold bootstrap resampling of 500 patients treated at 3 centers, who comprised the development cohort and were tested in an external independent validation cohort of 166 patients at a fourth center. ResultsAmong the 500 patients who underwent liver resection of the development cohort, liver resection–surgical site infection occurred in 66 patients (13.2%), and the median time to diagnosis was 6.0 days (interquartile range, 4.0–9.0) days. Median C-reactive protein levels were significantly higher on postoperative day 1, postoperative day 3, and postoperative day 5 in the liver resection–surgical site infection group compared with the non–surgical site infection group (50.5 vs 34.5 ng/mL, 148.0 vs 72.5 ng/mL, and 128.4 vs 35.2 ng/mL, respectively; P < .001). Postoperative day 3 and postoperative day 5 C-reactive protein–level area under the curve values were 0.76 (95% confidence interval, 0.64–0.88, P < .001) and 0.82 (95% confidence interval, 0.72–0.92, P < .001), respectively. Postoperative day 3 and postoperative day 5 optimal cut-off values of 100 mg/L and 87.0 mg/L could be used to rule out liver resection–surgical site infection, with a negative predictive value of 87.0% (interquartile range, 70.2–93.8) and 76.0% (interquartile range, 65.0–88.0), respectively, in the validation cohort. ConclusionPostoperative day 3 and postoperative day 5 C-reactive protein levels may be valuable predictive tools for liver resection–surgical site infection and aid in hospital discharge decision-making in the absence of other liver-related complications.