At the request of the Administration for Strategic Preparedness and Response, the National Academies convened a committee to examine lessons learned from the COVID-19 pandemic and mpox multi-country outbreak to inform an evaluation of the state of smallpox research, development, and stockpiling of medical countermeasures (MCM). In the resulting report, the committee presents findings and conclusions that may inform U.S. Government investment decisions in smallpox MCM readiness, as well as the official U.S. position on the disposition of live viral collections at future World Health Assembly meetings.