OBJECTIVES:  To adapt and validate a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of orphan drugs in Catalonia (Catalan HealthService, CatSalut). METHODS:  Feasibility for adapting the EVIDEM framework to CatSalut was assessed using as reference the standard procedures of the CatSalut orphan drug evaluation and decision-making program (PASFTAC). During a workshop with PASFTAC members, framework criteria were adapted to the CatSalut context and weighted, using two different techniques to address uncertainty (5-points weighting technique and hierarchical allocation technique). A pilot drug assessment was done comparing the standard PASFTAC procedures versus EVIDEM methodology (evidence matrix and drug scoring). RESULTS:  The EVIDEM framework was feasible to be adapted to CatSalut. Most of the criteria were already considered in PASFTAC evaluation reports, and evidence was collected according to systematic literature review. Evidence reporting, criteria weighting and scoring were the main differences found. The EVIDEM framework was adapted by 16 PASFTAC members, including evaluators, decision-makers, clinical advisors and patient representative. The 13 quantitative criteria of the original framework were considered applicable to CatSalut. Out of the 7 Contextual criteria, 3 were considered as redundant/not applicable: “Mandate and scope of healthcare system”, “Environmental impact” and “Political/historical/cultural context”. “Population priorities and access” was clarified for decision-making purposes (“rare” or “ultra-rare” disease). Regarding weighting, the most important criteria for decision-making were (mean (SD)): “comparative effectiveness” (4.6 (0.5)), “disease severity” (4.5 (0.7)) and “unmet needs” (4.5 (0.5)). Criteria least important were “other medical costs” (2.9 (1.2)) and “size of affected population” (1.7 (1.2)). Same ranking occurred using the hierarchical weighting technique. CONCLUSIONS:  EVIDEM framework was considered a useful tool to complement the current CatSalut evaluation methods, contributing to standardisation and pragmatism, as well as facilitating healthcare decision-making discussions. The evidence matrix and criteria scoring were considered the most potentially applicable and useful tools to PASFTAC.