Background: The role of drug-resistance infections on surgical outcomes is controversial. The aim of the study was to determine whether increase antibiotic resistance was an independent risk factor for development of major non-infectious postoperative complications. Methods: This work included a multicenter cohort study of patients who underwent pancreatic resections for cancer over a 3-year interval. The primary outcome was major non-infectious complication rate developing after the occurrence of multi-drug sensitive (MDS) infection, multi-drug-resistant infection (MDR), and extensive drug-resistant (XDR) infection. Multivariate logistic regression models were used to adjust for patient and operative effects. Results: Eligible patients (517) were selected for the analysis. One hundred and thirteen (21.8%) patients had major non-infectious complications with a rate of 12.9% in the no infection group, 29.3% in the MSD, 41.5% in the MDR, and 58.8% in the XDR (p