Abstract Background: Approximately 25% of Philadelphia's sexually transmitted infections (STI) cases are among teens aged 15-19. Furthermore, there are increased rates of teen pregnancy in Philadelphia compared to other Pennsylvania counties. Lack of comprehensive sexual health education can leave youth vulnerable to various STIs and teen pregnancy. Proud Teens of Philly (PTOP) is a comprehensive sexual health education program for youth aged 12-19 to promote healthy choices and ultimately reduce sexual health disparities in Philadelphia. Methods: Participants were recruited from a network of partner sites such as public and charter schools, churches, and community-based organizations to attend eight 1-hour virtual synchronous sessions. An evidence-based comprehensive curriculum, Making Proud Choices (MPC), which aims to reduce risky behaviors was utilized. Pre- and post-surveys that examine intention to have sex, perceived susceptibility to STIs/HIV, and attitudes toward sex, condom use, and STIs were administered to 246 youth. Paired samples t-tests were used to evaluate changes before and after the program. Results: There were significant increases in positive attitudes towards condom use (pre=26.54, post=27.73, t=-2.18, p=0.03), more negative attitudes towards STIs/HIV (pre=7.62, post=6.65, t=5.22, p<0.001), and increased perceived susceptibility towards contracting STIs/HIV following the intervention (pre=4.41, post=5.39, t=-2.84, p<0.01). PTOP has successfully linked students to various local adolescent health clinics to bring resources directly to the students. An important lesson learned is the need for diverse facilitators to represent the diverse student populations we serve. Conclusion: The PTOP program was effective in promoting positive attitude towards condom use and STIs/HIV prevention behaviors. Its impact also expanded to teen advocacy and community capacity building. The systems thinking approach has shown to be critical in achieving sustainable changes in this high-risk population. Citation Format: Ra'Ann Merceir, Jade Truehart, Aisha Bhimla, Yin Tan, Jane Sileo, Lin Zhu, Min Qi Wang, Sabrina Liao, Julia Trout, Priya Nigam, Ellen Kim, Aimee Bogan, Grace X. Ma. An evidence-based sexual health education program to reduce STI and teen pregnancy rates in Philadelphia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B059.