Introduction. Despite recent advances in surgical techniques, pancreatic fistulas are common. We aimed to determine the role of C-reactive protein in the prediction of clinically relevant fistula development. Materials and Methods. Data from patients who underwent pancreaticoduodenectomy between 2012 and 2015 is collected. Postoperative 1st, 3rd, and 5th day (POD1, POD3, and POD5) C-reactive protein (CRP) levels, postoperative pancreatic fistula (POPF) development, other complications, length of hospital stay, and mortality were recorded. Results. Of 117 patients, 43 patients (36.8%) developed complications (including fistulas). Of the patients developing fistulas, 21 (17.9%) had POPF A, 2 (1.7%) had POPF B, and 7 (6.0%) had POPF C. POD5 CRP and POD3 CRP were shown to be significantly correlated with mortality and development of clinically relevant POPF (p = 0 001 and p = 0 0001, resp.) and with mortality (p = 0 017), respectively. The development of clinically relevant POPFs (B and C) could be predicted with 90% sensitivity and 82.2% specificity by POD5 CRP cut-off level of 19 mg/dL and with 100% sensitivity and 63.6% specificity by the difference between POD5 and POD1 CRP cut-off level of > 2.5 mg/dL. Conclusion. CRP levels can effectively predict the development of clinically relevant pancreatic fistulas.