BACKGROUND: We aim to determine if C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), and procalcitonin (PCT) in drain fluid can serve as screening tools for colorectal anastomotic leakage (CAL). METHODS: Patients included in this multicenter prospective observational study underwent left hemicolectomy, sigmoid resection, high anterior resection, low anterior resection, or subtotal colectomy. During the first 5 postoperative days, CRP, LBP, and PCT were determined on drain fluid. RESULTS: In total 243 patients were included, of whom 19 (8%) developed CAL. CRP levels were higher in patients with leakage on day 3 and day 5, levels of LBP were higher on days 2, 3, and 4, and PCT levels were higher on day 5. Multivariate analysis showed LBP to be significantly related to CAL. An increase in the average initial value at the first postoperative day with 1 standard deviation increased the risk of leakage by 1.6 times. CONCLUSION: Increased concentrations of LBP in drain fluid are significantly associated to a higher chance of CAL and could contribute in a future prognostic model for CAL. (C) 2014 Elsevier Inc. All rights reserved.