Policy-makers, implementing organizations, and funders of global health programs aim to improve health care services and health outcomes through specific projects or systemic change. To mitigate the risk of corruption and its harmful effects on those initiatives, health programs often use multiple anti-corruption mechanisms, including codes of conduct, documentation and reporting requirements, and trainings. Unfortunately, the introduction of anti-corruption mechanisms tends to occur without an explicit consideration of how each mechanism will affect health services and health outcomes. This may overlook potentially more effective approaches. In addition, it may result in the introduction of too many controls (thereby stymying service delivery) and a focus on financial or procurement-related issues (at the expense of service delivery objectives). We argue that anti-corruption efforts in health programs can be more effective if they prioritize addressing issues according to their likelihood and level of harm to key program objectives. Recalibrating the anti-corruption formula in this way will require: (i) extending responsibility and ownership over anti-corruption from subject experts to public health and health system specialists, and (ii) enabling those specialists to apply the Fraud Risk Assessment methodology to develop tailored anti-corruption mechanisms. We fill a documented gap in guidance on how to develop anti-corruption mechanisms by walking through the seven analytical steps of the Fraud Risk Assessment methodology as applicable to health programs. We then outline best practices for any anti-corruption mechanism, including a focus on quality health delivery; the alignment of actors’ incentives around the advancement of health objectives; and being minimally corruptible by design.