OBJECTIVES: The objective of this study is to analyze and compare the recommendation made by several countries for orphan drugs such as Canada, Scotland, Australia, France and England.The study will try to address solutions and innovative ways to evaluate orphan drugs from an economic perspective and try to propose the hallmarks of an ideal policy to be implemented. METHODS: The Orphanet website was screened to find orphan drugs with national designations.237 orphan drugs indication were retrieved and  36 technologies  were included in the study and  stratified by therapeutic areas.In total, 180 recommendations were analyzed for the 5 included HTA agencies. Each recommendation was analyzed for the following parameters: Listing, clinical recommendation, economic recommendation, QALYs and rarity of disease taken in consideration. RESULTS: Scotland (88%) was the country that took the most in consideration the orphan designation of drugs, followed by France (74%) and Australia (45%). In addition, France and Scotland were the 2 countries that had the most positive listings (with criteria or without). The clinical benefit was demonstrated in multiple drugs throughout the different agencies. However, the economic part was very heterogeneous. Scotland issued a lot of positive economic recommendations (60%); however countries such as Canada had a very low percentage of economic being accepted (19%). QALYs did not seem to correlate with the type of listing.Countries that had the most health policies regarding orphan drugs had a better rate of orphan drugs being accepted for reimbursement. CONCLUSIONS: Though there are certain similarities across countries with regards to the HTA of orphan drugs, significant differences exist, which are likely to continue to cause variations in access to orphan drugs across countries.  Positive listing by CADTH was one of the lowest between 5 countries and the economic recommendations were the most negative in Canada.Seperate funding for orphan drugs and specific clinical assessment should idealy be implemented throughout the world.