The costs of a hospital-wide selective screening programme were analysed for a period of 19 months. During this time, 539 inpatients were screened, of whom 111 were MRSA-positive. Based on microbiological costs (staff and materials) and the costs of preventive contact isolation for 2 days until microbiological results were available (including material costs for medical consumable goods and the costs of additional nursing time), a total of 26,241.51 Euro was spent for the 539 patients screened. Based on cost units, the costs were 39.96 Euro for a patient found to be MRSA-negative and 82.33 Euro for a patient found to be MRSA-positive. Under the prospective diagnosis related groups (DRG) payment system in Germany, the costs of a prolonged hospital stay resulting from a hospital-acquired MRSA infection (HA-MRSA-I) are not reimbursed adequately by revenues, with a calculated average cost-revenue loss/patient with HA-MRSA-I of 5705.75 Euro. The screening programme was able to prevent 48% of predicted HA-MRSA-Is (35.2 patients with infection), thereby saving a predicted 200,782.73 Euro. After subtracting the screening costs, there was a net saving of 110,236.56 Euro annually. A sensitivity analysis of the break-even points for different screening frequencies and different MRSA incidence rates indicated that the screening programme became cost-effective at a low MRSA incidence rate, meaning that it can be recommended for most hospitals with an MRSA problem.