Objectives: Traumatic brain injury (TBI) is preventable and expensive. The medical costs of TBI can be too high for some households and might lead to poverty, malnutrition, and loss of assets, which are called catastrophic expenditures. In this study, we investigated the incidence of catastrophic costs associated with TBI caused by road accidents in a province in northern Iran. Methods: This prospective study involved a 1-year follow-up after the accident. Data of 220 patients were collected from the medical records of the Poursina Hospital, Rasht, Iran from March 2018 to February 2020. Direct and indirect costs faced by the households of patients with TBI and catastrophic costs related to TBI were calculated. Regression models were obtained and sensitivity analyses were performed at the end of the study. Results: In total, the prevalence of households TBI-related catastrophic costs (TBICC) was 45.5% . Households of female patients (odds ratio [OR]: 0.289, p=0.042), households of retired patients (OR: 0.053, p=0.005), and households falling in the fifth quintile of wealth (OR: 0.370, p=0.050) faced lower TBICC compared to other groups. The Activities of Daily Living scores had a significant negative relationship with TBICC. Conclusions Political interventions such as implementation of insurance schemes, exemptions from payment for certain groups, identification of poor households, and coverage of assistance services can protect households from catastrophic health expenditures.