ABSTRACT.- There is a need for rigorous and scientifically-based testing standards for existing and new enteric methane mitigation technologies, including antimethanogenic feed additives (AMFA). The current review provides guidelines for conducting and analyzing data from experiments with ruminants intended to test the antimethanogenic and production effects of feed additives. Recommendations include study design and statistical analysis of the data, dietary effects, associative effect of AMFA with other mitigation strategies, appropriate methods for measuring methane emissions, production and physiological responses to AMFA, and their effects on animal health and product quality. Animal experiments should be planned based on clear hypotheses, and experimental designs must be chosen to best answer the scientific questions asked, with pre-experimental power analysis and robust post-experimental statistical analyses being important requisites. Long-term studies for evaluating AMFA are currently lacking and are highly needed. Experimental conditions should be representative of the production system of interest, so results and conclusions are applicable and practical. Methane-mitigating effects of AMFA may be combined with other mitigation strategies to explore additivity and synergism, as well as trade-offs, including relevant manure emissions, and these need to be studied in appropriately designed experiments. Methane emissions can be successfully measured, and efficacy of AMFA determined, using respiration chambers, the sulfur hexafluoride method, and the GreenFeed system. Other techniques, such as hood and face masks, can also be used in short-term studies, ensuring they do not significantly affect feed intake, feeding behavior, and animal production. For the success of an AMFA, it is critically important that representative animal production data are collected, analyzed, and reported. In addition, evaluating the effects of AMFA on nutrient digestibility, animal physiology, animal health and reproduction, product quality, and how AMFA interact with nutrient composition of the diet is necessary and should be conducted at various stages of the evaluation process. The authors emphasize that enteric methane mitigation claims should not be made until the efficacy of AMFA is confirmed in animal studies designed and conducted considering the guidelines provided herein. © 2025, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®.