Objectives: To compare characteristics of caregivers of adults with acute traumatic brain injury (TBI) in the U.S. and Latin America (Mexico and Colombia). Design: Secondary data analysis of two cohorts. Cohort 1: English-speaking caregivers of adults with TBI in the U.S. (n = 80). Cohort 2: Spanish-speaking caregivers of adults with TBI in Mexico or Colombia (n = 109). Results: Similarities between the U.S. and Latin American caregiver groups, respectively, were: predominantly women (81.3%, 81.7%, respectively); spouses/domestic partners (45%, 31.2%); and motor vehicle accident (41.5%, 48.6%) followed by fall etiologies (40%, 21.1%). Differences between U.S. and Latin American caregivers were: age (49.5 years, 41.5 years, p < 0.001); employment status ((Χ₅² = 59.63, p < 0.001), full-time employment (63.7%, 25.7%), homemaker (2.5%, 31.2%), and retired (17.5%, 1.8%)); violence-related etiology (2.5%, 15.6%); and severity of depressive symptoms (M = 7.9, SD = 5.8; M = 5.8, SD = 5.7; p = 0.014). Conclusions: TBI caregivers in the U.S. were older and employed full-time or retired more often than those in Latin America. Violence-related etiology was nearly five times more common in Latin America, raising concerns for potential implications of post-traumatic stress and family adjustment after injury. Although both groups likely could use mental health support, this was particularly true of the U.S. cohort, maybe due to differential demographics, mechanisms of injury, or family and community support.