Background: Road traffic crashes (RTCs) are the leading injuries-related cause of death worldwide. A clear dose-effect relationship has been demonstrated for drugs and/or substances use and traumatic brain injury (TBI). Objectives: The objective of this study was first to estimate the prevalence of drug and substances use in traumatic brain injuries casualties. Second to assess TBI severity by selected assessment prognostic tools. Subject &Methods: The study was conducted from January 2014 to March 2015, where 1200 cases of both sexes were examined after RTCs. Toxicological screening and confirmatory tests were done for all cases to detect drugs and substance abuse. The initial severity of TBI was assessed by Glasgow coma score GCS and modified Marshall Classification. The clinical outcome was evaluated according to Glasgow Outcome Score (GOS), intensive care unit (ICU) & hospital length of stay (LOS). Results: Head injuries account for (110) 9.17 % of cases. Eighty eight cases (80%) were confirmed positive for substance use after hospital admission. Severe head injuries group account for 48/54 cases while 40/ 56 were with less severe head injuries. At the time of crashes tramadol was positive in forty cases (36.4%), cannabis was positive in twenty one cases (19.1%),alcohol was positive in eleven cases (10% ), amphetamine was positive in five cases (4.5 %), cocaine and sedative hypnotics were positive in one case(0.9%) and nine cases were positive for multiple substances (8.1%). Both GCS and modified Marshall Classification revealed that there was no statistical significant different in sociodemographic characteristic. However, confirming significant difference in relation to ICU, hospital LOS and GOS, which was more evident in Marshall assessment. Visible diffuse injuries as described by Marshall was observed in 77 patients (70%). In this study, 10/110 patients had undergone neurosurgery intervention. Using sensitivity and positive predictive value; in positive drug testing group, Marshall classification giving in more and less severe head injury a sensitivity 44%, 47% and positive predictive value 57%, 34% respectively in comparative to GCS. The relation was significant (P 0.003). In the negative drugs testing group, there was complete agreement between severe GCS and Marshall. As for agreement between mild or moderate GCS and less severe Marshall .These indicated that severity of head injury was relatively more accurate using Marshall classification in comparison with GCS which was affected by drug and substances abuse. The clinical outcome of patients revealed that 93 cases (84.5%) underwent good recovery, 7 (6.4%) moderate disability, and 5 (4.5%) died in early days. Conclusion: Drugs and Substance abuse among road traffic casualties influence the severity of TBI and clinical outcome. Recommendations: Modified Marshall classification is more sensitive as an early prognostic tool, so it is recommended to use it for the assessment of TBI severity induced by the influence of drugs and substance abuse intoxication.