This quasi-experimental study explores 575 secondary technical school students' knowledge on AIDS after a short health education program in Assiut City. Students were recruited using two-stage stratified cluster sampling and completed an anonymous, self-administered questionnaire. Pre and post testing was used to identify changes in knowledge. Only 30.8% students had satisfactory knowledge on AIDS prior to the health program. Statistically significant increases in knowledge were found after program implementation (P0.001). Muslim students, those living in urban areas, and those with mobile phones had greater knowledge. Common misconceptions related to defining AIDS according to transmission and phobias related to transmission. These were reduced, although comparatively less than knowledge levels were increased, after the program. Multivariate analysis revealed that age, religion and exposure to the health education program were significant predictors of changes in knowledge. More health programs that are tailored to local cultural concepts and values are needed to improve knowledge and dispel misconceptions.