Rapidly scaling up the use of prescribed fire is being promoted as an important pathway for reducing the growing damages of wildfire events in the United States, including limiting the health impacts from smoke emissions. However, we do not currently have the science needed to understand how the health impacts associated with prescribed fire smoke in the present compare to wildfire smoke exposure in the future. In particular, we lack an understanding of how the potential long-term public health benefits of prescribed fire on future wildfire smoke and health impacts compare to prescribed fire’s short-term effects on human health. Answering the question ‘How do we learn to sustainably coexist with wildfire?’ requires a new research agenda investigating the magnitudes and distribution of the health benefits and costs associated with prescribed burning. We suggest three areas for a new research agenda: (1) improved understanding of the health costs of prescribed fire; (2) quantification of the expected health benefits of prescribed fire through possible decreased future wildfire smoke emissions; and (3) better knowledge on the distributional impacts of prescribed fire smoke. We conclude that we need to first learn to sustainably coexist with prescribed fire in order to sustainably coexist with wildfire.