Abstract Road traffic accidents have been responsible for an increasing number of deaths and disabilities worldwide. Aim: Assess knowledge and practice of car drivers regarding first aid of road traffic accident. Subjects and methods: A cross-sectional research design was used in the study. It was conducted at Sohag University. A 87 Car drivers was participated in this study. Two tools developed by the researcher were used: Tool:the first tool: A structured interviewing questionnaire that include two parts; Part 1: demographic data of car drivers. Part 2: knowledge assessment questionnaire about first aid and road traffic accidents. Second tool: An observational checklist was used to assess practices of drivers regarding first aid of road traffic accidents. Results: The mean age of the participants was 43.36 ± 9.48. 33.3% of them had secondary education. 92.0% of them weren't having previous first aid training. 86% of them had an unsatisfactory knowledge level and all of studied car drivers had unsatisfactory practices of first aid of road traffic accident. Conclusion: The current study concluded that the majority of them had an unsatisfactory knowledge level and total of car drivers had unsatisfactory practices of first aid of road traffic accident Recommendations: Design and implement training programs for car drivers regarding first aid of road traffic accidents.