BackgroundPancreaticoduodenectomy is the standard treatment for resectable periampullary cancer. Surgical site infections (SSI) are common complications with increased morbidity. The study aimed to describe the prevalence, risk factors, microbiology, and outcomes of SSI among patients undergoing pancreaticoduodenectomy. MethodsWe conducted a retrospective study in a referral cancer center between January 2015 and June 2021. We analyzed baseline patient characteristics and SSI occurrence. Culture results and susceptibility patterns were described. Multivariate logistic regression was used to determine risk factors, proportional hazards model to evaluate mortality, and Kaplan-Meier analysis to assess long-term survival. ResultsA total of 219 patients were enrolled in the study; 101 (46%) developed SSI. Independent factors for SSI were diabetes mellitus, preoperative albumin level, biliary drainage, biliary prostheses, and clinically relevant postoperative pancreatic fistula. The main pathogens were Enterobacteria and Enterococci. Multidrug-resistance rate in SSI was high but not associated with increased mortality. Infected patients had higher odds of sepsis, longer hospital stay and intensive care unit stay, and readmission rate. Neither 30-day mortality nor long-term survival was significantly different between infected and non-infected patients. ConclusionsSSI prevalence among patients undergoing pancreaticoduodenectomy was high and largely caused by resistant microorganisms. Most risk factors were related to preoperative instrumentation of the biliary tree. SSI was associated with greater risk of unfavorable outcomes; however, survival was unaffected.