Risk factors of human-related traffic crashes are the most important and preventable challenges for community health due to their noteworthy burden in developing countries in particular. The present study aims to investigate the role of human risk factors of road traffic crashes in Iran. Through a cross-sectional study using the COM 114 data collection forms, the police records of almost 600,000 crashes occurred in 2010 are investigated. The binary logistic regression and proportional odds regression models are used. The odds ratio for each risk factor is calculated. These models are adjusted for known confounding factors including age, sex and driving time. The traffic crash reports of 537,688 men (90.8%) and 54,480 women (9.2%) are analysed. The mean age is 34.1 ± 14 years. Not maintaining eyes on the road (53.7%) and losing control of the vehicle (21.4%) are the main causes of drivers’ deaths in traffic crashes within cities. Not maintaining eyes on the road is also the most frequent human risk factor for road traffic crashes out of cities. Sudden lane excursion (OR = 9.9, 95% CI: 8.2–11.9) and seat belt non-compliance (OR = 8.7, CI: 6.7–10.1), exceeding authorised speed (OR = 17.9, CI: 12.7–25.1) and exceeding safe speed (OR = 9.7, CI: 7.2–13.2) are the most significant human risk factors for traffic crashes in Iran. The high mortality rate of 39 people for every 100,000 population emphasises on the importance of traffic crashes in Iran. Considering the important role of human risk factors in traffic crashes, struggling efforts are required to control dangerous driving behaviours such as exceeding speed, illegal overtaking and not maintaining eyes on the road.