OBJECTIVES: In recent years, health technology assessment (HTA) agencies have encountered substantial technical challenges in assessing the relative value of new therapies for multiple sclerosis (MS), potentially delaying patient access to promising drugs. We assessed the impact of contrasting approaches to HTA in Germany and the UK on patient access to new therapies for MS. METHODS: Technology appraisals performed by the National Institute for Health and Care Excellence (NICE) and Institute for Quality and Efficiency in Healthcare (IQWiG) since the Pharmaceuticals Market Reorganisation Act (AMNOG) in January 2011 were assessed. Quantitative and qualitative assessment of appraisal decisions in the context of overall assessment processes, evidence requirements and anticipated patient impact were conducted for each technology. RESULTS: Three therapies have been assessed by both NICE and IQWiG (fingolimod, dimethyl fumarate and teriflunomide); both bodies have assessed additional therapies independently. All three technologies were recommended by NICE in restricted patient populations, with an agreed price discount. NICE faced considerable technical methodological challenges during the assessment process, including comparator selection (blended versus pair-wise incremental analyses), assessment versus non-cost-effective beta-interferon comparators and appropriate use of mixed treatment comparisons. In some cases, modelling assumptions accepted in previous appraisals were criticised by NICE in subsequent submissions. By contrast, IQWiG and the Federal Joint Committee (G-BA) concluded that all drugs provided no proven clinical benefit, except fingolimod (minor benefit in limited subset of patients with rapidly-evolving severe relapsing-remitting MS), due to limited clinical data versus IQWiG-specified comparators. CONCLUSIONS: Patients in Germany can access all three therapies, consistent with their marketing authorisations, despite the negative IQWiG appraisal recommendations. In the UK, however, fewer patient subgroups can access the same therapies, partly due to evolving methodologies used by NICE to assess cost-effectiveness. Greater understanding of challenges that impact HTA decisions may facilitate earlier patient access to promising MS therapies.