Introduction: Road traffic accidents (RTAs) represent a leading contributor to the global disease burden. Drivers involved in some RTAs were found to be under the influence of different drugs. Marijuana effects on driving risks are not thoroughly understood. The study aimed to compare the pattern, severity, and clinical outcome of injuries between marijuana-smoking drivers and non-drugged drivers in RTAs. Patients and Methods: This prospective, comparative study was carried out on 78 drivers admitted to the emergency department, Tanta University Emergency Hospital during the period from the start of January to the end of December 2018. All drivers were subjected to history taking, clinical examination, assessment of injury severity score (ISS) and revised trauma score (RTS), and detection of tetrahydrocannabinol (THC) in urine. Results: Thirty-six drivers tested positive for THC with a median level of 314.6 ng/ml. There was a lack of significant association between marijuana smoking and the site of injuries. The marijuana-positive group had a significantly higher frequency of skull fractures, ruptured spleen, intraperitoneal hemorrhage, and abrasions on the body surface when compared to the marijuana-negative group. The median ISS was non-significantly higher, and the mortality was significantly higher in the marijuana-positive group. The THC level correlated significantly and strongly with both ISS and RTS. A significantly higher median THC level was detected in non-survivors compared to survivors. Conclusion: It could be concluded that Marijuana smoking is associated with an increased mortality rate in victims of RTAs. There are strong correlations between THC level and both ISS and RTS, suggesting a dose-dependent effect of marijuana smoking.