OBJECTIVES: Postoperative thrombosis is a common complication after major orthopaedic surgery. Standard prophylaxis is done with subcutaneous injections of low molecular heparin. Oral anticoagulants became available for this indication in the last years. It was the aim of this study to develop a modelling matrix considering all types of costs in order to allow for a cost-benefit-analysis comparing anticoagulants in the post-operative setting. METHODS: This study is a prospective, comparing clinical observation study. 90 patients after total hip/knee replacement were included. Quality of life (QOL) was measured by an specific score (PACT-Q®). Also the compliance was analyzed (Morisky). Clinical/labdata as well as information on occurrence and reason of readmittance to the hospital were collected. This analysis evaluates the cost-benefit-ratio of the oral anticoagulant rivaroxaban compared with subcutaneous low molecular weight heparin certoparin-sodium from the German patients’ and society`s perspective RESULTS: For this study a new method was developed. The result is a matrix, which calculates the corrected total costs (Cc) by multiplication of direct costs (CD) with a factor FQOL representing QOL. FQOLis the difference between optimal and actual quality of life (in). By this method, the effect of QOL and compliance on total costs and on the value of a therapy becomes visible. By application of two anticoagulants it became apparent, that the corrected costs for rivaroxaban where lower (22,1%) than its direct costs, resulting in a sum advantage for the innovative drug, although direct costs were higher (9,7%) for the oral drug. CONCLUSIONS: Medicaments enter the market with mostly higher prices compared to the standard. The payers should evaluate, if the more expensive pharmaceutical product saves costs during the therapeutical pathway or if the result generates a higher quality of life for the patients which could mean better compliance with less costs for following treatments.