Increasingly advanced medicines have created monopolies in treatment areas with no viable options for generic substitution due to patent protection. As health care systems are increasingly under pressure to deliver health care improvements, costs become prohibitive as budgets are under pressure. To create financial flexibility, Danish regional authorities have over the period from 2009 until today developed, implemented, and gradually increased the use of a new model for analogue medicine substitution. The model introduces competitive tenders among patented medicines by declaring these medicines therapeutically equivalent in the treatment of specific diseases and thereby creating new opportunities for reducing annual medicine expenses. The model is based on enhanced collaboration among the health technology assessment (HTA) body, the procurement body, and the hospital owner, and it effectively covers medicine expenditure and cost-effectiveness while ensuring standardized treatments across hospitals and regions. The model is internationally unique in integrating several healthcare stakeholders and balancing their respective agendas to generate optimized outcomes for the healthcare system as a whole. However, some challenges persist, as the HTA process is resource and time consuming. Future research can show whether there are other challenges connected with the model.