Emergency research poses a fundamental ethical dilemma: prohibit valuable research because informed consent is not possible or enroll individuals in clinical trials without informed consent. Although emergency research without initial consent is allowable in the United States, its regulatory status remains uncertain internationally. More important, no ethical justification for emergency research without consent has been widely accepted. Whether emergency research without initial consent can be justified depends on whether the values that are secured by informed consent—respect for autonomy and protection of well-being—can be secured by other means. Analysis suggests that these values can be secured by the satisfaction of 5 conditions: (1) responsiveness (the experimental intervention must be responsive to an urgent medical need of the patients), (2) comparable risk-benefit ratio (the risk-benefit ratio of the experimental intervention is favorable, and at least as favorable as that of available alternatives and the control, if any), (3) no conflicting preferences (there is no compelling reason to think that participation in the research conflicts with enrolled patients' values or interests), (4) minimal net risks (nonbeneficial procedures included in the study cumulatively pose no greater than minimal risk), and (5) prompt consent (consent for ongoing and additional emergency research interventions is obtained as soon as possible). Together, these conditions constitute an ethical substitute for informed consent in emergency research—forming the consent substitute model.