OBJECTIVES: A surrogate endpoint (SE) is an indicator variable substituting for a clinically meaningful endpoint that reflects how a patient feels, functions or survives. These include physiologic variables that are indicators of normal biological/pathogenic processes or pharmacological responses to an intervention and can also be biomarkers. Use of SEs requires decision-makers to consider their relevance when determining clinical benefit and pricing. Although SEs have been discussed by several research initiatives, little coverage is devoted to how different decision-makers deal with value uncertainty and how this translates into access and price across indications and markets. The purpose of this study was to examine HTA assessments of SEs across indications and markets to inform recommendations on optimising evidence generation when dealing with SEs. METHODS: RESULTS: Variability exists in the acceptability of SEs for payer decision-making across markets and indications, driven by assessment methodologies, strategies for managing uncertainty and the level of clinical consensus supporting the SE. There is however awareness of the need to accommodate SEs to support early market access with greater flexibility in assessment protocols.  CONCLUSIONS: Selection of a SE requires careful consideration of the rationale linking the SE to clinical benefit and strategies for managing uncertainty. This will require a tailored approach to payer value communication addressing market and indication specific expectations for clinical relevance.