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Septic complications after pancreatic surgery are common. However, it remains unclear if and how a shift of the microbiological spectrum affects morbidity. The aim of the present study was to assess the microbiological spectrum and antibiotic resistance patterns and their impact on outcome.We conducted a retrospective study including patients undergoing pancreatic surgery at our center between 2005 and 2018. A systematic literature review and descriptive meta-analysis of the published and original data was performed according to the PRISMA guidelines.A total of 318 patients were included in the analysis. Patients with biliary drainage had a significantly higher incidence of bacterobilia (93% vs. 25%) and received preoperative antibiotics (46% vs. 12%). The analyzed bile cultures showed no resistance to piperacillin/tazobactam, fluoroquinolones, or carbapenems. Resistance to cefuroxime was seen in 58% of the samples of patients without biliary drainage (NBD) and 93% of the samples of those with drainage (BD). In general, there was no significant difference in overall postoperative morbidity. However, superficial surgical site infections (SSIs) were significantly more common in the BD group. We included a total of six studies and our own data (1627 patients) in the descriptive meta-analysis. The percentage of positive bile cultures ranged from 53 to 81%. In patients with BD, the most frequent microorganisms were Enterococcus spp. (58%), Klebsiella spp. (29%), and E. coli (27%). Almost all studies demonstrated resistance to first- and second-generation cephalosporins and to third- and fourth-generation cephalosporins for patients with BD.A change in perioperative antibiotic strategy according to local resistance patterns, especially after BD, might be useful for patients undergoing pancreatic surgery. Appropriate perioperative antibiotic coverage may help to prevent abdominal infectious complications and especially superficial SSIs.