Introduction: According to The Egyptian Central Agency for Public Mobilization and Statistics (CAPMAS), 72% of road traffic accidents occur due to aberrant driving behavior. Substance abuse particularly cannabis is commonly used among Egyptian commercial drivers and seriously affects safe driving. Aim of work: To assess the magnitude of substance abuse among a sample of professional minibus drivers, Zagazig city, Sharqia Governorate, Egypt, to investigate their driving behavior and to determine the predicting factors for the risky driving behavior as a major cause of road accidents. Materials and Methods: A cross sectional study was conducted in Al Ahrar main public station, Zagazig city, Sharqia Governorate, Egypt on a sample of 130 commercial drivers. A structured questionnaire was introduced to all participants and included data on socio occupational status and the driving behavior questionnaire (DBQ) which is composed of 26 items. Substance abuse was screened through rapid assessment urine test. Results: Among the participants, 57.7% tested positive for substance abuse and the most common abused substance was cannabis which represented 80% of the positive participants. The DBQ scores were higher among substance abused drivers with statistical significant difference particularly in most of violations and error items. The predictors for aberrant driving behavior were low income, excessive speeding, previous involvement in road traffic crash and substance abuse. Conclusion: Illicit drugs are commonly used by Egyptian professional drivers and seriously affect safe driving. Regular traffic police campaigns for screening of substance abuse among commercial drivers and applying of road safety awareness program can lower the prevalence and burden of road traffic accidents in Egypt.