Purpose: To determine the relationship of illnesses and medical drug consumption with the occurrence of traffic accidents among truck and bus drivers. Methods: This is a cross-sectional study on truck and bus drivers in Tehran, Iran. The criteria for participating in this study were: married males over 30 years old, driving license in grade one, five years of job experience, mental health and non-addiction license. The criterion for not participating in this study was the lack of cooperation in responding to the questions. Six months was spent to collect the latest five years data of driving accidents from 2011 to 2016. A total of 323 truck and bus drivers in Tehran city and the suburbs, Iran were chosen. Among them, 112 were responsible for accidents (accident group) while 211 were not responsible for any accidents or involved in an accident in the last five years (non-accident group). A specially designed questionnaire was used to investigate the demographic informa-tion, medical drug consumption, medical backgrounds and history of accidents. Results: The results revealed that compared with healthy subjects, the occurrence of accidents among people with diabetes (OR = 2.3, p = 0.001) and vision weakness (OR = 1.7, p = 0.020) was significantly higher, while that among people with cardiac (OR = 0.5, p = 0.002) and hypertension (OR = 0.9, p = 0.048) problems was remarkably lower. Moreover, consumption of Gemfibrozil (OR = 1.8, p = 0.010) and Glibenclamide (OR = 2.2, p = 0.002) drugs resulted in significantly higher incidence of accidents than those without. Conclusion: Frequencies of illnesses like cardiovascular and hypertension were not higher in accident drivers than in non-accident drivers; but diabetes, vision weakness and consumption of Gemfibrozil and Glibenclamide lead to more traffic accidents.