Background: The integration of reproductive health (RH) into national strategies and programs is one of the targets of the Sustainable Development Goals (SDGs) adopted by the United Nations General Assembly in September 2015. Objective: Assessment of the effectiveness of an educational program on reproductive health knowledge of preparatory school female students in Alexandria Governorate.   Methods: A pre-post study design was conducted on 102 preparatory school female students by using a pre-designed self-administered questionnaire, covering four RH domains: puberty and menstrual cycle, genitourinary and sexually transmitted infections (STIs), menopause and female genital mutilation (FGM), as a tool for assessment of their RH knowledge before and after 6 weeks of applying an educational program for them. Results: The results revealed that the total RH knowledge of the female students improved significantly after intervention, as 64.7% of participated girls had a satisfactory level of knowledge after the educational program compared to zero % before intervention. The four RH domains: puberty and menstrual cycle, genitourinary infections, menopause and female genital mutilation all showed significant increase in their knowledge score percentage after intervention. Conclusion & Recommendation: RH educational program had a significant effect on the level of knowledge of the girls, thus we may recommend the integration of such education in the main school curriculum for the sake of improving their reproductive health.