The study aims to investigate the prevalence of alcohol and illicit drugs in Road Traffic Accident fatalities from January 2015 to December 2019 in Eastern region -Saudi Arabia. From a total of 1939 deaths investigated in the Dammam Poison Control Center, only 57 of them were related to Road Traffic Accidents (RTA), of which 96.4% were males, 36.8% were in the age group between 18-30 years. The highest incidence was among Saudi nationals (82.5%). 70.2% of the investigated cases tested positive for ethanol either alone or with other illicit drugs, cannabis ranked the second (38.6%), followed by amphetamine (17%) and heroin (10%). Ethanol was the sole toxicological finding in (57.5%). The single drug-abusing pattern (50.9%) exceeded bi-and triple drug-abusing pattern (31.5 %). None of the investigated samples showed a positive result for illicit cocaine or benzodiazepines. In Conclusion, ethanol identified as a key element, being the highest frequently detected substance in the blood samples of RTA victims which mandates the need for planning appropriate interventions and more strict application of Saudi national program for drug prevention together with wide community action.