OBJECTIVES: The goal of this project was to develop and apply an extended framework for evidence assessment based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach using the example of male human papilloma virus (HPV) vaccination Europe. METHODS: A pan-European multidisciplinary expert group was established to develop an extended GRADE framework that includes explicit assessment of cost-effectiveness, medical needs, and patient aspects, ethical and social issues. Using an expert panel process, we assessed the feasibility of using this framework by applying it to male HPV vaccination in Europe. Studies were assessed using the specific framework tools; results and feasibility were discussed; and consensus was achieved through a modified Delphi method. RESULTS: We identified three advisory committees (ACIP/USA; NACI/Canada; STIKO/Germany) using GRADE for vaccines assessment. Institutions handled data beyond vaccine efficacy and safety differently and did not formally grade economic evidence. We adopted the grading methodology of ACIP for the key factor ‘Benefits and Harms‘ and developed modules for grading evidence type and quality of economic evaluations (‘Economic Evaluation’) and for systematically assessing epidemiology, disease burden and unmet medical needs, as well as ethical, social and patient aspects (‘Values and Preferences’). The feasibility test demonstrated that all framework components were feasible in the case of HPV vaccination. Overall evidence type for cost-effectiveness was low with uncertainty in results. Cost-effectiveness was best, when all HPV-related diseases and outcomes were included and when assuming low coverage in females and lower vaccine prices. CONCLUSIONS: The GRADE approach is applicable in assessing vaccinations and was successfully applied to HPV vaccination in males. The assessment of benefits and harms can be extended by explicit assessment of the evidence on cost-effectiveness and other key factors including unmet medical needs, and ethical, social and patient aspects. This extended framework can better inform policy- and decision-makers.