OBJECTIVE: Post-operative infections are associated to increase of mortality and morbidity. The objective of this study was to estimate the hospital cost of antibiotic therapy in patients undergoing colorectal cancer surgery and the possible influence of infections in hospital cost. METHODS: We conducted a naturalistic, longitudinal, retrospective study, considering data from medical records of all patients undergoing colorectal surgery in 2002 at the Surgical Division of the IRCCS “S. de Bellis” of Castellana Grotte. RESULTS: Data from 83 patients (mean age 68.6, from 38 to 92 years, 48.2% men) were collected. In order to prevent infections, when the intervention started, and for at least the 48 hours, all patients but one (a patient allergic to antibiotics) were treated with 5-nitroimidazole and/or cephalosporin. If infections occurred, they were treated with one or more antibiotics: quinolones, carbapenems, amynoglicosides, cyclosporines and penicillines, according to the type of complication. Seventeen patients (20.5%) had post-operative infections, with a higher frequency in older patients (mean age 73.6 vs 67.3, P=0.024). Drug therapy cost (expressed as €/hospitalization) to the hospital was 206.0€ (0.0€–849.2€), for the most part attributable to prophylactic therapy: a mean of 178.1€ was spent for prophylaxis, while a mean of 28.5€ were spent for therapy administered if infection occurred. In patients with infections the average cost (362.5€) was more than twice than cost for patients without infections (166.3€). On average drug cost accounted for 3.7% of hospitalisation reimbursements. The average post-operative length of stay was sensitively longer in patients with infections (10 vs. 18 days, P<0.0001). CONCLUSIONS: A therapeutic strategy aimed at preventing chirurgical infections can accelerate patients’ remission, with repercussion on drug and hospital cost.