Background Cohort studies play essential roles in assessing causality, appropriate interventions. The study, Post-crash Prospective Epidemiological Research Studies in IrAN Traffic Safety and Health Cohort, aims to investigate the common health consequences of road traffic injuries (RTIs) postcrash through multiple follow-ups. Methods This protocol study was designed to analyse human, vehicle and environmental factors as exposures relating to postcrash outcomes (injury, disability, death, property damage, quality of life, etc). Population sources include registered injured people and followed up healthy people in precrash cohort experienced RTIs. It includes four first-year follow-ups, 1 month (phone-based), 3 months (in-person, video/phone call), 6 and 12 months (phone-based) after crash. Then, 24-month and 36-month follow-ups will be conducted triennially. Various questionnaires such as Post-traumatic Stress Disorder Questionnaire, Patient Health Questionnaire, WHO Disability Assessment Schedules, Cost-related Information, etc are completed. Counselling with a psychiatrist and a medical visit by a practitioner are provided accompanied by extra tools (simulator-based driving assessment, and psychophysiological tests). Through preliminary recruitment plan, 5807, 2905, 2247 and 1051 subjects have been enrolled, respectively at the baseline, first, second and third follow-ups by now. At baseline, cars and motorcycles accounted for over 30% and 25% of RTIs. At first follow-up, 27% of participants were pedestrians engaged mostly in car crashes. Around a fourth of injuries were single injuries. Car occupants were injured in 40% of collisions. Discussion The study provides an opportunity to investigate physical-psychosocial outcomes of RTIs, predictors and patterns at follow-up phases postinjury through longitudinal assessments, to provide advocates for evidence-based safety national policy-making.