Background: There has been a substantial increase in the conduct of natural experimental evaluations in the last ten years. This has been driven by advances in methodology, greater availability of large routinely collected datasets, and a rise in demand for evidence about the impacts of upstream population health interventions. amenable to natural experimental evaluation. It is important that researchers, practitioners, commissioners, and users of intervention research are aware of the recent developments. This new framework updates and extends existing MRC guidance for using natural experiments to evaluate population health interventions. Methods: The framework was developed with input from three international workshops and an online consultation with researchers, journal editors, funding representatives, and individuals with experience of using and commissioning natural experimental evaluations. The objective was to identify any additional content, unnecessary content, any topics of contention, and whether there were any revisions required to the structure of the guidance.

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