Background Several recent studies have investigated the role of C‐reactive protein (CRP) as an early marker of anastomotic leakage following colorectal surgery. The aim of this systematic review and meta‐analysis was to evaluate the predictive value of CRP in this setting. Methods A systematic literature search was performed using MEDLINE, Embase and PubMed to identify studies evaluating the diagnostic accuracy of postoperative CRP for anastomotic leakage following colorectal surgery. A meta‐analysis was carried out using a random‐effects model and pooled predictive parameters were determined along with a CRP cut‐off value at each postoperative day (POD). Results Seven studies, with a total of 2483 patients, were included. The pooled prevalence of leakage was 9·6 per cent and the median day on which leakage was diagnosed ranged from POD 6 to 9. The serum CRP level on POD 3, 4 and 5 had comparable diagnostic accuracy for the development of an anastomotic leak with a pooled area under the curve of 0·81 (95 per cent confidence interval 0·75 to 0·86), 0·80 (0·74 to 0·86) and 0·80 (0·73 to 0·87) respectively. The derived CRP cut‐off values were 172 mg/l on POD 3, 124 mg/l on POD 4 and 144 mg/l on POD 5; these corresponded to a negative predictive value of 97 per cent and a negative likelihood ratio of 0·26–0·33. All three time points had a low positive predictive value for leakage, ranging between 21 and 23 per cent. Conclusion CRP is a useful negative predictive test for the development of anastomotic leakage following colorectal surgery. Day 3 to 5 levels helpful