Cardiology has been a leading field in generating evidence through large randomized clinical trials (RCTs). The principle of clinical equipoise is widely endorsed as a foundational ethical requirement governing design and conduct of RCTs.1 Clinical equipoise encompasses 2 ethical considerations that are sometimes conflated but are logically distinct. First, for an RCT to be ethical, there must be genuine uncertainty about the scientific question that the trial is designed to answer. Second, RCTs are unethical if they randomize patients to an intervention known or believed by the expert clinical community to be inferior to the established standard of care. Clinical equipoise has intuitive appeal, especially because no one disagrees with the need for uncertainty. However, the practical implications of strict adherence to clinical equipoise in cardiology trials have not received critical attention.