Road Traffic Injuries (RTIs) represent a major global health problem. Substance abuse is a major contributing factor for such injuries. The current study aimed to investigate the problem of substance misuse among cab-drivers involved in non-fatal accidents. This cross-sectional study carried out at Al-Azhar University Hospitals (Cairo, Al-Hussein and Bab El-Sharia Hospitals), during the period from August 2012 to August 2014. All cab-drivers who were admitted to the emergency department with non-fatal motor car trauma were asked to participate. We identified 80 eligible drivers, 20 of them refused to participate. Thus, the final included cases were 60 drivers. Positive cases were 32 with an incidence rate of 53.3%. All were males. Socio-demographic factors were documented and urine samples were drawn to screen for abused substances (e.g., opiate, methamphetamine, tetrahydrocannabinol, barbiturates, benzodiazepines and tramadol). The most common abused substance was cannabis (THC) (90.6%), then tramadol in 59.4%, barbiturates in 34.4%, opiates in 28.1%, benzodiazepines in 25% and finally methamphetamine in 21.9%. In addition, 90.6% abused two or more substances concomitantly and 9.4% had a single substance. This study highlighted the magnitude of substance abuse in cab-driver. The most common abused drug was cannabis and the least was methamphetamine. The majority of cases (90.6%) abused more than one substance.