OBJECTIVES: To estimate the impact of initial empiric antibiotic treatment failure on pharmacological and total health care costs in hospitalized patients with cIAIs. METHODS: The economic impact associated with initial empiric antibiotic treatment failure was based on the results of an observational epidemiological study involving 201 adults with cIAI in Greece (NCT00929643). An average per patient-per day DRG value was estimated based on diagnosis at discharge and DRG mapping. Daily cost was then extrapolated to the additional length of stay (LOS), associated with initial antibiotic failure. Costs included expenditure for additional ICU and surgical interventions. DRG matching was validated by a specialist medical advisor. Mean per patient DRGs were weighed against subject percentage in each diagnosis group. Mean per patient costs for unsuccessful initial therapies were calculated using the latest formulary prices and the mean number of days on each antibiotic agent, as recorded in the observational study.  RESULTS: The most frequently reported diagnoses (201 subjects) were perforation of the intestine (15.9%), acute appendicitis with peritoneal abscess (13.4%) and post–operative peritonitis (13.4%). Patients most commonly received metronidazole (59.2%), followed by b–lactamase inhibitors (38.3%) and second generation cephalosporines (30.3%) as empiric antibiotic treatment (as part of monotherapy, double therapy or triple therapy schemes). 78 patients exhibited failure of the initial treatment, whereas initial treatment was successful in 111 subjects with respective hospitalization of 21.9±16.4 and 8.9 ± 4.5 days. Total additional per patient resource cost was estimated to be €3,761.56 inclusive of unsuccessful mean empiric antibiotic expenditure, which was estimated to be €220.06 per patient. CONCLUSIONS: Retrospective data collected for a 2-year period showed that a significant percentage (42.9%) of patients exhibited failure of their initial antibiotic treatment. These patients had a greater chance of requiring prolongation of hospitalization and more extensive use of healthcare expenditure during times where resources are scarce.