Objective: The aim of this present study was to evaluate mental health status of professional and unprofessional drivers in road car accidents resulted to severe human damage or death (serious accidents) in Iran. Methods: In this cross-sectional study, we evaluated 453 drivers who were condemned in mentioned car accidents, using convenient sampling method. The study was conducted from March, 2006 to December, 2006. The fields of study were road police stations, all through the country. Evaluation was done within the first 24 hour of accident. All drivers completed a demographic questionnaire and revised form of Symptom Checklist 90 (SCL-90-R). We used Farsi version of SCL-90-R which has reliability of 80-97%. Data were analyzed using SPSS software and descriptive statistics (mean, standard deviation (SD) and frequency), chi square test and T test for independent samples. We calculated odds ratio (OR), with 95% confidence interval (CI), as indicated. Type I error (&alpha) was set at 0.05. Findings: There was not any statistically significant different between professional and unprofessional drivers in SCL-90-R subscales. Mean (±SD) Global Symptom Index (GSI) in professional and unprofessional drivers was 0.86±0.58 and 0.86±0.55, respectively. In addition, GSI was higher than cut of point for normal Iranian population (0.81) for both groups. Totally, 209 drivers (46.1%) had GSI higher than 0.81. Odds ratio (OR) for having GSI higher than 0.81 for professional groups was 0.904 (95% CI: 0.566-1.444). Mean (±SD) Positive Symptom Total (PST) scores in professional was 45.8±24.5 and in unprofessional was 47.7±22.9. Mean (±SD) Positive Symptom Distress Index (PSDI) in two groups were 1.6±0.43 and 1.5±0.42, respectively. There was not any statistically significant difference between two groups, according to these three scores. In both groups, the mean score for paranoid ideation, obsession and compulsion, interpersonal sensitivity and depression subscales were higher than other subscales. Sixty-three of 106 drivers who hah history of previous serious car accident and 43 of 335 individuals who had not such history had GSI higher than 0.81 (p=0.001). OR was 2.12 (95% CI: 1.36-3.30). OR for having higher GSI among who used medicines related to sleepiness was 2.01 (95% CI: 1.14-3.53). Results: The study shows that mental health problems and using medicine (especially sedatives and hypnotics) may result in higher probability of serious car accidents. It seems that intervention in such domains may be beneficial to prevent such accidents.