Introduction Hospital supply chains are complex systems ensuring flow of products/services to satisfy patients. The aim of this exploratory study is to improve the Maltese health care system’s efficiency using supply chain management principles in three hospital settings. The theoretical basis underlying the study is the supply chain decision-making framework. Methods Using observation and focus groups, the following steps were undertaken: (i) mapping healthcare supply chain processes and identifying challenges; (ii) understanding competitive strategy through implied demand uncertainty; (iii) deriving supply chain strategies through supply chain drivers; (iv) optimizing healthcare supply chain (right balance between cost and responsiveness); (v) identifying critical success factors for healthcare supply chains. Results In line with their competitive and supply chain strategies, the three settings have well-defined primary goals, stakeholders’ needs/demands/expectations, as well as clear-cut, albeit some similar, criteria and sub-criteria for improving the quality and quantity of their services. The trade-offs between efficiency and responsiveness for the supply chain drivers are distinctive and in line with their competitive strategies, hence achieving the desired fit with the healthcare supply chain strategies. Conclusions By adopting healthcare supply chain principles, there should be improved services in each setting, which in turn should lead to system-wide results.