Costs related to a search and destroy policy and treatment for Staphylococcus aureus bacteraemia in the University Hospital Maastricht were calculated for the period 2000 and 2004. The financial cost-benefit break-even point of the search and destroy policy was determined by modelling. On average 22,412 patients were admitted per year for an average of 8.7 days. Each year 246 patients were screened for meticillin-resistant Staphylococcus aureus (MRSA) and 74 patients were decolonised and nursed in preventive isolation. The prevalence of MRSA in the University Hospital Maastricht was 0.7%, as calculated from positive blood cultures, and mean length of stay for all patients with S. aureus bloodstream infections was 39.9 days. The annual cost of pro-active searching for MRSA in the University Hospital Maastricht was euro 1,383,200, and euro 2,736,762 for MRSA prevention and treatment of S. aureus bloodstream infections. Simulation of a variety MRSA/meticillin-susceptible S. aureus (MSSA) ratios showed that even if the MRSA prevalence reaches 8%, prevention costs are still lower than the cost of treating S. aureus infections. In conclusion, the total cost of a search and destroy policy is lower than the cost of treating S. aureus bloodstream infections in the University Hospital Maastricht. At an MRSA prevalence of <or=8% the search and destroy policy remains cost-effective. From an economic point of view, the search and destroy policy is the best alternative at maintaining an endemic MRSA level at <1%.