<b><i>Introduction:</i></b> The impact of acute inflammation on cancer progression is still not well elucidated. Pancreatic head cancer is occasionally associated with acute cholangitis. C-reactive protein (CRP) is a biomarker that indicates presence of acute inflammation. <b><i>Methods:</i></b> We reviewed the patients’ data with pancreatic ductal adenocarcinoma (PDAC) who underwent pancreaticoduodenectomy between 2004 and 2018. <b><i>Results:</i></b> Two hundred ninety-one patients were included. Median preoperative CRP was 0.45 mg/dL (0–18.9). Median follow-up duration was 22 months (4–152). The 1-, 3-, and 5-year overall survival (OS) rates were 76.4%, 32.2%, and 22.9%, respectively. Recurrence occurred in 168 cases (57.7%). The 1-, 3-, and 5-year disease-free survival (DFS) rates were 53.9%, 27.1%, and 21.9%, respectively. The median OS was higher in normal CRP patients (27 months) than those with elevated CRP (18 months) (log-rank 0.038). The median DFS was higher in normal CRP patients (17 months) than those with elevated CRP (9 months) (log-rank < 0.001). Predictive factors for OS included BMI, CRP, adjuvant therapy, positive lymph nodes, and microvascular invasion. Predictive factors for DFS included CRP, positive lymph nodes, and microvascular invasion. <b><i>Conclusion:</i></b> Preoperative CRP was an independent poor prognostic factor for OS and DFS of patients with resected PDAC.