Piperacillin-tazobactam reduces surgical site infections compared to cefoxitin, impacting long-term surgical outcomes for pancreatoduodenectomy patients.

• Patients on piperacillin-tazobactam had lower surgical site infection rates, improving postoperative recovery.
• No significant differences in chemotherapy omission rates between the two antibiotic groups (9.4% vs. 15.4%).

Surgical site infections correlated with poorer 3-year overall survival (HR 1.69).

Improving antibiotic prophylaxis can enhance patient outcomes and inform treatment strategies.