Background: School students are at high risk of being injured or facing life-threatening conditions. So, improving their knowledge about first aid is essential. Objective(s): To assess first aid knowledge and its determinants among primary school students in Alexandria and measure the level of their knowledge after first aid educational program. Methods: A cross-sectional study followed by a pre- /post-test intervention was conducted on fourth to sixth grade students from the eight districts of Alexandria, who were selected by a multistage random sample technique. Students were invited to fill out a questionnaire to assess their knowledge regarding first aid. Then, educational sessions were conducted using different methods such as group discussions, case scenarios, and visual aids. Finally, students' knowledge was assessed after the educational program. Results: The current study involved 372 (154 males and 218 females) primary school students with a mean age of 11.49 ± 0.93 years. Among the 15 questions used for assessing the knowledge of students, there was a deficiency in the knowledge about dealing with swallowing a chemical substance, burns, snake bites, epistaxis, bleeding, fractures, and sunstroke. These shortages improved significantly after the educational program. There was a highly statistically significant improvement in first aid knowledge score among the students, from 48.8 ± 11.5% to 87.4 ± 14.6 after the educational program. This improvement was also highly significant among males, females, the different districts and class grades, as well as among those having or not having a working father or mother. Conclusion: School aged children showed high improvement in their knowledge regarding first aid dealing with swallowing a chemical substance, burns, snake bites, epistaxis, bleeding, fractures, and sunstroke after the application of an educational program.