Background: Sacred Beginnings is a community-based participatory research project that examines the effectiveness of a culturally appropriate preconception health educational intervention developed by tribal community members and elders. The primary goal is to increase knowledge of preconception health and its benefits among adolescent females and tribal communities. Preconception health is an area of considerable concern among American Indians (AIs) in the Northern Plains region, as there are high rates of birth, infant mortality, unintended pregnancy, teen pregnancy, and sexually transmitted diseases in this area. We examined the effectiveness of implementing this intervention during a residential summer program for AI high school students. Materials and Methods: The educational intervention consisted of 15 preconception health education sessions and was piloted during a summer high school residential academic program. The intervention (N = 39) and non intervention (N = 38) groups were comprised of incoming AI female freshmen representing comparable demographics. A pre- and post-intervention survey was administered to both groups. Results: Results indicated a significant difference in Time 2 (T2; post-intervention) scores, with the intervention group scoring higher than the non-intervention group in overall preconception health knowledge and obesity knowledge. In terms of intra-group score analysis between Time 1 (T1; pre-intervention) and T2, there were significant changes within the intervention group in knowledge of obesity and diabetes. Knowledge changes in smoking were approaching significance. Within the non-intervention group, there was a significant change from T1 to T2 in scores for diabetes knowledge only. Discussion: The key finding was that the intervention group had higher overall preconception health knowledge at T2 compared to the non-intervention group. Intervention participants demonstrated an understanding of how preconception behaviors may affect birth outcomes and maternal health. Another key finding was that, among participants in the intervention group, the change in knowledge regarding smoking beliefs between T1 and T2 were approaching significance. Because smoking during pregnancy is a risk factor for poor birth outcomes, this finding emphasizes that future curriculum modification should address the effects of smoking, and the benefits of smoking cessation, prior to or during pregnancy. Study limitations such as small sample size, high baseline health knowledge, the need to add traditional knowledge variables, and shortened implementation timeframe reveal key areas for improvement. Possible future intervention modifications include expanding on areas that reached or approached significance, implementing the intervention over a longer period of time, identifying ways to translate traditional knowledge into quantifiable survey measures, and implementing the intervention with high-risk, reservation-based populations of AI youth. (Contains 3 tables.)