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To examine and compare the use of health technology assessment (HTA) for the reimbursement of new medicines in selected European Union member states with decades of experience in the use of HTA and in countries that have used it regularly since 2000. Methods: The selected countries were categorized into "earlier" adopters (group A: England, Germany, France, and Sweden) and more "recent" adopters (group B: Poland, Bulgaria, Hungary, and Romania). A systematic review of published literature was performed. The analysis and comparison of HTA procedures were done by using an analytical framework. Results: In all countries, the assessment criteria used include effectiveness, safety, relative effectiveness, and economic data. In group A countries, the main objectives are improving quality of care, ensuring equal access, and efficient use of resources. Group B countries have established HTA organizations with official guidelines but often seek the decisions of other developed countries. They place considerable emphasis on the budget impact of new therapies, and HTA is also used as a cost estimation tool for state budgets. Conclusions: HTA organizations have been developed dynamically not only in high-income countries but also in countries with limited resources. The experience and evolution of both can be used by countries that are in the dawn of creating an HTA organization.