OBJECTIVES: Health technology assessments (HTAs) varies by regulatory authorities. Four cancer and five hepatitis C drugs with a high financial impact were evaluated in eight HTA agencies; AETSA (Spain), AIFA (Italy), CADTH/pCODR (Canada), C2H (Japan), HAS (France), IQWiG (Germany), NICE (UK), and PBAC (Australia), to understand differences in decision process and criteria. METHODS: Two types of sources were examined: HTA dossiers from eight HTA agencies’ websites and the HTA Accelerator (HTA dossier platform by IQVIA). 28 factors were chosen to be evaluated by previous research review; clinical factors that were identified as having uncertainties/issues by the authorities, consideration factors classified as disease, population and treatment including NICE’s criteria factors for special circumstances (e.g. end-of-life, stakeholder persuasion, innovation), and value elements by ISPOR Special Task Force. A qualitative and quantitative analysis (correspondence analysis) were conducted to assess the differences across agencies. RESULTS: The highest clinical uncertainties were observed for clinical benefits followed by comparator. As for cancer drug consideration factors and NICE’s factors, correspondence analysis showed HAS, PBAC, pCODR, and NICE considered the most factors with common items such as unmet needs, stakeholder persuasion, disease nature/severity, and indirect benefits. NICE is the only agency to consider end-of-life, issues around current treatment and innovation. IQWiG has a high association with manageable or insignificant adverse events. Finally, for the value elements, PBAC is unique as they consider fear of contagion, equity and scientific spillover. CONCLUSIONS: Although clinical factors play a predominant role in the decision to reimburse medicine, HTA agencies consider additional aspects that can influence the final outcome of the evaluation. Overall, NICE and PBAC considered the most factors relative to other agencies despite limitations of the publicly available content of HTA dossiers. If methodology of HTA was clearly outlined, there would be more transparency in HTA systems leading to better understanding amongst stakeholders about decision-making.