OBJECTIVES: Hospitals need a formalized system to introduce new health technologies. Hospital-based HTA (HB-HTA) units can provide relevant and timely information to decision makers. However, to date no comprehensive body of knowledge of current practices and tools exists to guide how to set up these units in hospitals. AdHopHTA, a European research project funded by theFP7, aims to gather information and knowledge and develop these tools. Therefore, our objectives are to present the handbook and web-based toolkit for HB-HTA developed by the AdHopHTA project, which aims to guide and facilitate the setting-up and the daily work (e.g. assessments) of an HB-HTA unit. METHODS: AdHopHTA has used a multi-method approach to develop the content of the handbook and toolkit including 6 literature reviews, 107 face-to-face surveys, 40 case studies, 1 large-scale survey, 1 focus group, 1 Delphi process, 1 validation workshop and several Steering and Advisory Committee meetings. In total 375 people from 20 different countries have provided their input. RESULTS: The handbook presents the informational needs and organizational models of HB-HTA units in Europe. It also describes the positive impact of HB-HTA in the adoption of new health technologies in hospitals and how to create a comprehensive HTA ecosystem through the interaction between national or regional HTA organizations and HB-HTA units. 15 guiding principles for good practices in HB-HTA are also presented using current examples from existing HB-HTA units. The Toolkit is built based on these guiding principles. It consists of practical guidance grouped into four dimensions (the assessment process; leadership, strategy and partnerships; resources and  and impact). It includes proposed solutions to potential problems as well as specific tools (e.g. AdHopHTA mini-HTA template) for each dimension. CONCLUSIONS: The AdHopHTA Handbook and Toolkit are support instruments for designing,  setting-up and running HB-HTA units.