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Background The widening gap between population health needs and available resources is placing intense pressure on the English health system. As a result, health leaders are increasingly presented with difficult trade-offs. While extensive literature outlines the principles that should guide priority setting, there is limited empirical evidence on how health leaders justify the decisions they make in practice.Methods This qualitative study involved semi-structured interviews with a range of senior health leaders (n=11) representing various national, regional, and local organisations across the English health system. The interviews examined how leaders navigate challenging trade-offs, such as those between preventative health measures and acute care services. Data were analysed using reflexive thematic analysis.Results There was a consensus among participants regarding the key principles that should guide priority-setting decisions, including equity, efficacy and cost-effectiveness. In practice, however, justifications for decisions sometimes diverged from these principles owing to emotional biases, political constraints and structural barriers. Despite strong rhetorical support for greater preventative health measures, these influences tended to favour decisions which prioritised short-term over long-term health outcomes. When faced with difficult trade-offs, differences were observed in how participants prioritised key principles and ethical considerations, with notable divergences between health leaders with clinical and non-clinical backgrounds.Conclusion This study highlights the gap between the justifications leaders give in principle and those they apply in practice when priority setting. The findings suggest that real-world approaches of senior health leaders may, over time, inadvertently jeopardise the long-term financial sustainability of the NHS by favouring immediate over future population health outcomes. The differences in approach between clinical and non-clinical leaders underline the importance of considering who is involved in resource allocation decisions to ensure diverse perspectives are represented.