Health technology assessments (HTAs) are used as a policy tool to appraise the clinical value, or cost effectiveness, of new medicines to inform reimbursement decisions in health care. As HTA organisations have been established in different countries, it has become clear that the outcomes of medicine appraisals can vary from country to country, even though the same scientific evidence in the form of randomised controlled trials is available. The extant literature explains such variations with reference to institutional variables and administrative rules. However, little research has been conducted to advance the theoretical understanding of how variations in HTA outcomes might be explained. This paper compares cases of HTA in England and Germany using insights from Kuhn (1962, The Structure of Scientific Revolutions, 2nd edn. Chicago: The University of Chicago Press) and Hall (1993, Policy paradigms, social learning, and the state: the case of economic policymaking in Britain. Comparative Politics 25, 275–296) to demonstrate how policy paradigms can explain the outcomes of HTA processes. The paper finds that HTA outcomes are influenced by a combination of logical issues that require reasoning within a paradigm, and institutional and political issues that speak to the interaction between ideational and interest-based variables. It sets out an approach that advances the theoretical explanation of divergent HTA outcomes, and offers an analytical basis on which to assess current and future policy changes in HTA.