BACKGROUND: Evidence bases medicine is the governing principle ruling all aspects of a new medical product. Marketing authorization organizations and health technology agencies focused on the reimbursement aspects of a new product are both relying in their decision making process on clinical data of the highest possible evidence. While marketing authorization is an increasingly international process with standardized rules, the reimbursement process is conducted on a national level with country-specific requirements. In some indications, e.g. in chronic diseases, where it is difficult to recruit newly diagnosed patients for clinical trials, establishing the efficacy of a product against placebo is a common approach, as only patients who did not succeed with the available treatment options are willing to participate in these trials. OBJECTIVES: To review the national requirements for the reimbursement of new medical products with a positive centralized marketing authorization based on placebo-controlled clinical trials. We will demonstrate that the acceptance of placebo-controlled trials is handled differently between countries and that different strategies to process these data are necessary. METHODS: We focused on the national health technology agencies of five representative European countries, including the United Kingdom, France, Germany, Sweden and the Netherlands. A targeted desktop research on the published methodology and the decisions regarding medical products with a marketing authorization based on placebo controlled trials for the most recent years was conducted. RESULTS: The methodological requirements to get reimbursement for a medical product with a marketing authorization based on placebo-controlled trials are different in these countries, leading to heterogeneous decisions. CONCLUSIONS: Getting a positive decision for reimbursement is challenging for products which have marketing authorization based on placebo-controlled trials. The national requirements and thresholds for reimbursement are very different and highly dependent on the governing principle for evaluation, ranging from quality of life based decisions to comparator driven additional benefit decisions.