Objectives: The objective is to explore how HTA frameworks can be considered as a tool for pharma to rethink their processes and organisation in order to improve commercial success for innovative products. Methods: Firstly, we explore the variety of HTA framework, to identify which should be used in this study. In parallel a literature search discusses the complexity of pharmaceutical organizational models: owner managed (type 1), functional (type 2), divisional (type 3), or matrix. A review of initiatives undertaken by pharmaceutical companies to align operations based on HTA frameworks, is conducted. Finally the critical assessment of these initiatives relies on the methods and tools provided by the Theory of Organizations. Results: EUnetHTA’s framework appears to be the right research material since it is EU-wide, and more mature than other international frameworks (AsiaLink and RedETSA). The most advanced initiative undertaken by pharma in terms of aligning the company with HTA frameworks was conducted by Roche. The analytical tools we use suggest to explore organizations along various dimensions: environmental (simple vs. complex and static vs. dynamic) and internal aspects (tangible elements: structure, technology, strategy and people – non tangible elements: culture, managerial vision, performance). Initiatives conducted by pharma have in fact focused on the technical dimensions (i.e. EUnetHTA’s framework as an “incomplete” check list). General principles ensuring successful organizations transformation for HTA frameworks alignment were identified and we show that much remains to be done to align operations in terms of the structure, technology, strategy and even implications on performance. Conclusions: As of today, HTA frameworks have been considered by pharma mostly as a check list to increase the likelihood of positive opinions. Aligning operations with HTA frameworks should imply a much deeper business transformation: from structure to technology, also with a revised perspective on the group’s strategy and performance indicators.