PROJECT SUMMARY This study, “Cradling Our Future Long-Term (16-year) Follow-Up,” will determine if a culturally tailored, evidence based early childhood home visiting intervention, called “Family Spirit®,” reduces long-term substance use, suicide, and related consequences among Indigenous mothers and their children16 years after they exited the program (at 3 years postpartum). Substance use and suicide comprise the largest and most devastating health inequities for American Indians and are the result of generations of racial trauma and oppression. Family Spirit was designed over an 8-year period specifically for and by American Indian communities through an intensive community based participatory process to promote behavioral and mental health across two generations. The original “Cradling Our Future” study (NIDA R01 DA019042-01A1) was a 1:1 randomized controlled trial that enrolled N = 322 expectant teen mothers by 32 weeks gestation and followed them and their children to 3 years postpartum. Mothers randomized to the intervention group received culturally tailored home visiting lessons delivered by local American Indian paraprofessionals focused on positive parenting and content addressing maternal stress, substance use, and depression. The control condition was transportation to prenatal and well-child visits and facilitated connections to community resources, which mothers in both the intervention and control arms received. Trial results demonstrated Family Spirit significantly improved parenting efficacy, reduced marijuana and illicit drug use and depressive symptoms in mothers, and improved social, emotional, and behavioral development for children until 3 years postpartum in ways that would predict less substance use and lower suicide risk and related problems across teen mothers' and youth's developmental life course. Based on this evidence, home visitors and supervisors have been trained to implement Family Spirit in over 150 tribal and additional non-tribal communities across the US, but long-term impacts of this and other home visiting programs on problematic substance use, overdose, and suicide are vastly understudied. The aims of this follow- up study are to identify long-term impacts of Family Spirit on mothers' (at 30-39 years old) and their children's (at 18-19 years old) substance use and suicidal thoughts and behaviors, while exploring moderators (i.e., discriminatory stress, cultural engagement) and mediators (i.e., continued positive parenting) of effects. We will also use qualitative narrative inquiry methodology to explore individual and intergenerational drug use pathways (e.g., first use, misuse, polydrug use, pre-addiction, abstinence, recovery) with a sub-sample of participants. If favorable long-term impacts are found, findings could leverage federal support for evidence-based home visiting implementation that is still under-utilized in tribal communities. Tribal populations deserve greater evidence for effective cultural strengths-based solutions to redress lasting behavioral and mental health effects of colonization and racism.