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Purpose Despite to high burden of road traffic injuries (RTIs), the RTI epidemiology has received less attention with rare investments on robust population cohorts. The PERSIAN Traffic Safety and Health Cohort (PTSHC) was designed to assess the potential causal relationships between human factors and RTI mortality, injuries, severity of the injury, hospitalised injury, violation of traffic law as well as offer the strongest scientific evidence.Participants The precrash cohort study is carried out in four cities of Tabriz, Jolfa, Shabestar and Osku in East Azerbaijan province located in northwest Iran. The participants were people who sampled among the general population. The cluster sampling method was used to enrol the households in this study. The PTSHC encompasses a wide and comprehensive range and types of data. These include not only the common cohort data collections such as medical examination measures, previous medical history, bio assays and behavioural assessments but also includes data obtained using advanced novel technologies, for example, electronic travel monitoring, driving simulation and neuro-psycho-physiologic laboratory assessments specifically developed for traffic health field.Findings to date A total of 7200 participants aged 14 years and above were enrolled at baseline, nearly half of them being men. The mean age of participants was 39.2 (SD=19.9) years. The majority of participants (55.4%) belonged to the age group of 30–56 years. Currently, approximately 1 200 000 person-measurements have been collected.Future plans PSTHC will be used to determine the human-related risk factors by adjusting for the vehicle and land-use-related factors. Therefore, a lot of crashes can be prevented using effective interventions. Although this cohort provides valuable data, it is planned to increase its size to achieve the highest level of evidence with higher generalisability. Also, according to the national agreement this cohort is going to be extended to several geographical regions in second decade.