This chapter investigates the economic impact of surgical site infections (SSIs) on Italy’s National Health Service (NHS), highlighting the burden of SSIs on healthcare expenditure and patient care. Using Hospital Discharge Records from 2015 to 2021, the prevalence and economic consequences of SSIs across surgeries for diseases such as diverticulitis, appendicitis, cholecystitis, cholelithiasis, hernia, and ventral hernia were analyzed. The study focused on the extended hospital stays and additional costs associated with SSIs, estimating the economic burden on the NHS. The analysis included over 893,000 surgeries, identifying an average SSI rate of 0.23%, ranging from 0.07% and 1.35%. It was found that SSIs extended hospital stays by an average of 13 days and increased NHS costs by €4424 per admission, reflecting in a total economic burden of €18.8 million over the study period. SSIs have a significant epidemiological and economic burden on the NHS, underscoring the need for improved infection prevention and control measures. The study advocates for the implementation of more effective surgical protocols and practices to reduce the prevalence of SSIs, thereby enhancing patient outcomes and reducing the economic burden on the healthcare system.