OBJECTIVES: Both the HTA Core Model® (CM) for pharmaceutical evaluations and the Academy of Managed Care Pharmacy (AMCP) Format (Format) for formulary submissions were developed to streamline health technology assessment (HTA). The CM is specific to European HTAs, while the Format is specific to US managed care. This study aims to compare these approaches to identify areas of overlap, and differing elements that may reflect regional values and preferences.  METHODS: The CM for pharmaceuticals (Version 2.1) and the Format (Version 3.1) were examined and analyzed by two reviewers. A table of 17 characteristics was created to evaluate which elements align or do not align. RESULTS: Of the 17 characteristics, 5 were found to be aligned, 5 were somewhat aligned, and 7 were not at all aligned. The CM provides more detailed guidance (388 pages of guidance, 447 pages total) on desired data sources and rationale, whereas the Format provides only a short overview of requirements and methodology (17 pages of guidance, 95 total).  There is general alignment in terms of requiring information on burden of disease, existing treatment options, clinical effectiveness, and economic analyses, however within these overarching themes, certain variations exist. For example, the CM suggests cost-effectiveness, -utility or -benefit analyses, while the Format suggests only cost-effectiveness analyses. In addition, the CM contains additional sections, including ethical analysis, organizational aspects, social aspects, and legal aspects. Alternatively, the Format contains an addendum specific to use of comparative effectiveness research (CER), as defined in the US, stipulating that CER studies reflect patient preferences. It also contains a separate addendum specific to specialty pharmaceuticals. CONCLUSIONS: While the CM and Format require similar information to be submitted, certain regional values and health system differences are reflected in the varying approaches. Trans-Atlantic collaboration could be helpful in standardizing characteristics across these frameworks.