Policies in the United States and beyond are driving efforts to phase out the use of Aqueous Film Forming Foam (AFFF) products used to extinguish flammable liquid fires at airports, military complexes, oil and gas operations, industrial facilities, and municipal firefighting operations. AFFF contains per- and polyfluorinated alkyl substances (PFAS), which are highly persistent, bioaccumulative and toxic substances. This guidance outlines specific criteria to evaluate and determine whether alternatives are safer as compared to current PFAS-containing AFFF products. The criteria should be considered the minimum requirements for a safer AFFF alternative determination. Criteria are drawn from existing approaches, in particular the Organization for Economic Cooperation and Development’s “Guidance on Key Considerations for the Identification and Selection of Safer Alternatives” and supplemented by others such as the Green Screen CertifiedTM for Fire Fighting Foam and the US Environmental Protection Agency’s Safer Choice criteria. This guidance is not a detailed protocol for conducting a hazard assessment; it assumes that users have the necessary toxicological expertise and practicing knowledge for conducting such assessments. Users should recognize that some state, local, or tribal governments in the United States may have additional requirements that should be considered when choosing safer firefighting foams.