OBJECTIVES: Health Technology Assessment (HTA) agencies require various types and qualities of evidence for clinical effectiveness evaluations due to differences in healthcare systems and policies. It is essential for manufacturers to understand these requirements when submitting an application to each individual HTA agency. METHODS: A literature search of clinical recommendations from the following HTA agencies was conducted for comparison: CADTH (Canada), HAS (France), IQWiG (Germany), NICE (England), PBAC (Australia), PHARMAC (New Zealand) and SMC (Scotland). RESULTS: The choice of the optimal comparator is crucial to the outcome of the HTA. Almost all agencies prefer comparison versus the most frequently used interventions except for PBAC which requires comparison to the interventions most likely to be displaced. All HTA agencies are cautious in their interpretation of surrogate outcomes (SO) and require manufacturers to provide evidence linking the SO to final patient-relevant outcomes. PBAC has notably developed a framework for assessing SOs and the impact of these on uncertainty in HTA submissions. Most agencies except for NICE clearly state their position on the definition and the use of SOs. All agencies recognize the value of observational studies in reflecting real-world situations and providing long-term data although RCTs provide the key evidence on comparative effectiveness. Systematic reviews (SR) of clinical evidence are essential to present comparative effectiveness relative to all comparators. Contrary to most agencies, HAS prefers SRs but does not require them and bases its assessments mainly on pivotal clinical trials provided by the manufacturer. NICE and IQWiG also differ from the other agencies as they perform in-house SR in addition to the manufacturer’s. CONCLUSIONS: The differences between agency requirements are subtle and mean that manufacturers need to put together a solid clinical evidence package needing very little adaptation to meet the seven country requirements.