Major resections for esophageal, gastric, hepatic, pancreatic, and colorectal cancer continue to be associated with a high peri-operative morbidity of up to 30%–40%. To a large extent, this morbidity is caused by infectious complications that add up to a considerable burden to patients and hospital costs. The objective of this large retrospective cross-sectional study was to determine independent patient and operation-related risk factors for infectious complications after major abdominal cancer operations to elucidate how infection rates can be reduced and improve health-care quality. In this study, several independent risk factors for infectious complications in major abdominal cancer operations were identified, providing opportunities for further reducing peri-operative infections.