Background: Intervention effects observed in efficacy trials are rarely replicated when the interventions are broadly disseminated, underscoring the need for more information about factors influencing real-life implementation and program impact. Using data from the ongoing national implementation of an evidence-based HIV prevention program [Focus on Youth in The Caribbean (FOYC)] in The Bahamas, this study examines factors influencing teachers' patterns of implementation, the impact of teachers' initial implementation of FOYC, and subsequent delivery of the booster sessions on students' outcomes. Methods: Data were collected from the 80 government elementary and 34 middle schools between 2011 and 2014, involving 208 grade 6, 75 grade 7, and 58 grade 8 teachers and 4411 students initially in grade 6 and followed for 3 years. Student outcomes include HIV/AIDS knowledge, reproductive health skills, self-efficacy, and intention to use protection. Data from teachers includes implementation and modification of the curriculum, attitudes towards the prevention program, comfort level with the curriculum, and attendance at training workshops. Structural equation modeling and mixed-effect modeling analyses were applied to examine the impact of teachers' implementation. Results: Teachers' attitudes towards and comfort with the intervention curriculum, and attendance at the curriculum training workshop had a direct effect on teachers' patterns of implementation, which had a direct effect on student outcomes. Teachers' attitudes had a direct positive effect on student outcomes. Teachers' training in interactive teaching methods and longer duration as teachers were positively associated with teachers' comfort with the curriculum. High-quality implementation in grade 6 was significantly related to student outcomes in grades 6 and 7 post-implementation. Level of implementation of the booster sessions in grades 7 and 8 were likewise significantly related to subsequent student outcomes in both grades. Conclusions: High-quality initial implementation of a prevention program is significantly related to better program outcomes. Poor subsequent delivery of booster sessions can undermine the positive effects from the initial implementation while strong subsequent delivery of booster sessions can partially overcome poor initial implementation.