Objectives: This study evaluated the impact of methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired infection on postoperative complications and patient outcome after pancreatoduodenectomy (PD). Methods: Seventy-nine patients who underwent PD were monitored for hospital-acquired MRSA. The patients were grouped as (1) no MRSA infection, (2) skin colonization with MRSA, and (3) systemic MRSA infection. Results: Forty (51%) of the 79 patients were MRSA positive during hospital admission. Fourteen of the 40 patients swabbed for MRSA were found positive (skin colonization), and 26 patients (33%) developed systemic MRSA infection after PD. The sites of MRSA infection included (1) abdominal drain fluid (16/26; 42%), (2) sputum (4/26; 15%), (3) blood cultures (2/26; 8%), and (4) combination of sites (9/26; 35%). The patients with systemic MRSA infection had a longer postoperative stay (31 vs 22 days; P = 0.005) and increased incidence of chest infections compared with MRSA-negative patients (14 vs 4; P = 0.02). Four of the 16 patients with MRSA-positive drain fluid had a postpancreatectomy hemorrhage compared with 3 of the 63 patients with no MRSA infection in drain fluid (P = 0.02). Conclusion: Of the 79 patients admitted for PD, 51% became colonized with MRSA infection. Systemic hospital-acquired MRSA infection in 33% was associated with prolonged postoperative stay, increased wound and chest infections, and increased risk of postoperative hemorrhage.