Objectives: Retinal hemorrhage is a cardinal manifestation of abusive head injury. Thrombophilia is relatively common in the general population and in adults can be associated with retinal hemorrhage. The specificity of retinal hemorrhage for abusive head trauma in the presence of prothrombotic factors, in particular following non-abusive head trauma, has not been investigated. Our objective was to determine whether the hypothesis that prothrombotic factors affect specificity of retinal hemorrhage to AHT can be tested. This may have important ramifications both for diagnosis and expert witness testimony. Methods: To investigate the feasibility of studying this issue, we conducted a prospective cohort study of children with abusive and non-abusive head trauma. Thrombophilia screening and ophthalmic examinations were performed. Results: Six of 30 admitted children were fully enrolled. Enrollment obstacles included caregiver stress, animosity towards allegations of abuse, child protection services involvement, and research phlebotomy coordination. Prevalence of thrombophilia was high in children with retinal hemorrhage and in 1 case the question of hemorrhage adjudicated as abuse was considered in light of a history of a fall. Conclusion: We estimate that to answer the critical question of retinal hemorrhage specificity for abuse in the presence of thrombophilia will require 53 centers for a 1 year study or 18 centers for a 3-year study. We identify potential obstacles and interventions. (Contains 3 tables and 1 figure.)