New “cutting-edge” medical interventions generally transition from research to the clinical realm after initial studies resolve short-term equipoise, demonstrating greater benefit than harm. During this transition, new interventions’ potential long-term consequences remain uncertain, which is problematic for physicians attempting to obtain appropriately informed consent. In this study, physicians were interviewed regarding their perspectives on the informed consent process for a particular intervention (neonatal therapeutic hypothermia) at a particular historical moment after short-term equipoise had been resolved but before a definitive understanding of this therapy’s long-term consequences existed. Thirty neonatologists and pediatric neurologists at the Children’s Hospital of Philadelphia were interviewed using a structured tool that quantified agreement with general statements regarding neonatal therapeutic hypothermia and perceptions of different consent processes. Of these, 33% of physicians agreed that neonatal therapeutic hypothermia should only be initiated after obtaining signed informed consent, whereas 37% felt that hypothermia should be initiated as standard emergent treatment. Preference for a more stringent consent process did not correlate with concerns regarding the strength of evidence supporting the intervention, but rather with placing a high value on parental counseling and with believing that children who receive the intervention may be less likely to die but more likely to survive in a severely disabled state. Thus, physicians conceptualized how to obtain consent for a transitional intervention with uncertain long-term consequences based less on strength of evidence and more on concerns regarding their duty to counsel and the potential for long-term disability. We discuss possible solutions for clinicians approaching these challenges.