The amount of medical research with persons who lack decision-making capacity is rapidly increasing, but in most states it takes place without any legal authority. In addition to creating significant liability risks for researchers and persons who provide consent on behalf of incapacitated subjects, the lack of explicit legal standards means that few, if any, safeguards exist to protect incapacitated persons’ rights and welfare. Previous efforts to close the gap between clinical reality and legal requirements have failed in part because they have not provided a coherent or persuasive ethical justification for permitting this research. This Article fills that void by proposing a new way of thinking about the ethics of research with incapacitated persons, grounded in a long-term, systemic approach to risk-benefit assessment. This approach explains why it is ultimately in incapacitated persons’ best interests to be governed by a policy that permits them to be enrolled in research without their personal authorization—even if such a policy puts them at risk of participating in studies that, when viewed in isolation, may involve more burdens than benefits. Unlike other approaches, the framework developed here does not depend on false analogies between participating in research and receiving medical treatment, dubious claims about family members’ inherent authority, or incapacitated persons’ obligations to society. Because the proposed framework directly responds to the criticism that research with incapacitated persons is a form of exploitation, it increases the likelihood that proposals to authorize this research will actually be adopted. At the same time, it has important implications for both how laws governing research with incapacitated persons should be structured, and the roles and responsibilities of surrogate decision makers.