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Australians have high expectations of national cancer screening programs as effective tools for early disease detection. But are these expectations higher than warranted? While many people benefit from early diagnosis through screening, research shows that some screening tests may lead to a cascade of further tests and unnecessary, sometimes harmful, treatment. In this paper, we draw on qualitative interview data with Australian health professionals to explore their views on screening. Applying concepts from science and technology studies, we focus on the evidence-making processes through which screening is enacted as a beneficial population health strategy, asking how health professionals justify screening when the evidence is contested. While some of our participants emphasised the protective value of screening, others expressed mixed views about its benefits and risks, and we suggest this is linked to the evidentiary uncertainty surrounding screening. In conducting this analysis, the paper applies an ‘evidence-making intervention’ approach, which conceives evidence as produced through, and contingent on, the practices of science, policy and medicine. Challenging the dominant view that evidence comprises a stable body of knowledge which can be integrated into policy, our paper argues for closer scrutiny of how evidence is assembled to justify particular interventions and to manage uncertainty. While we explore these issues in the context of population-based screening, we also address their broader implications for the evidence-based policy endeavour as the dominant paradigm in Western healthcare settings.