Background: The aim of this study was to evaluate the effect of variables such as personality traits, driving behavior and mental illness on road traffic accidents among the drivers with accidents and those without road crash.Methods: In this cohort study, 800 bus and truck drivers were recruited. Participants were selected among drivers who referred to Imam Sajjad Hospital (Tehran, Iran) during 2013-2015. The Manchester driving behavior questionnaire (MDBQ), big five personality test (NEO personality inventory) and semi-structured interview (SADS) were used. After two years, we surveyed all accidents due to human factors that involved the recruited drivers. The data were analyzed using the SPSS software by performing the descriptive statistics, t-test, and multiple logistic regression analysis methods. P values less than 0.05 were considered statistically significant.Results: In terms of controlling the effective and demographic variables, the findings revealed significant differences between the two groups of drivers that were and were not involved in road accidents. In addition, it was found that depression and anxiety could increase the odds ratio (OR) of road accidents by 2.4- and 2.7-folds, respectively (P=0.04, P=0.004). It is noteworthy to mention that neuroticism alone can increase the odds of road accidents by 1.1-fold (P=0.009), but other personality factors did not have a significant effect on the equation.Conclusion: The results revealed that some mental disorders affect the incidence of road collisions. Considering the importance and sensitivity of driving behavior, it is necessary to evaluate multiple psychological factors influencing drivers before and after receiving or renewing their driver’s license.