This study had explored the top ten countries medicines expenditure and it was found that United Kingdom had the highest drop in spending by 2015. Preliminary investigations conducted found the reasons for this drop, focusing cost-containment initiatives on medicines expenditure practice. Further preliminary investigations also made to identify the region and participants, where and who the study should be conducted. These investigations used secondary analysis of data. Realistic evaluation framework used in this study to uncover the factors involved in the practice of cost-containment initiatives on medicines expenditure and their impact on the hospitals. The factors involved identified by what works, in what conditions, why and which outcomes. Elite interviewing conducted on chief pharmacists to identify these factors. From this study, cost-containment initiatives found to be complex with inter-related factors that could affect the savings made. In many respects, the organisations practised similar interventions nationally, regionally and locally. However, variations found in terms of setting priorities of cost-containment initiatives and measurement of cost-effectiveness. This study identified the decision-making process of chief pharmacists were mainly pragmatic that included local rationality in terms of politics in choosing which cost-containment initiative was to be prioritised and implemented. Various facilitators and barriers also found to affect the outcomes of the cost-containment initiatives. This study also acknowledged that chief pharmacists faced many pressures such as adhering to local and national polices to contribute towards cost-savings. As a result, this study had developed a model for cost-containment initiatives of medicines expenditure. The model summarised the context-mechanism-outcome configurations of the factors involved in the practice of cost-containment initiatives on medicines expenditure in the hospitals and their impact from the chief pharmacists’ point of view. It could become a feasible guideline for pharmacists in conducting, standardising the evaluation and implementation of cost-containment initiative. It would be useful as easy reference for future research.