Background: Evidence-based programs (EBPs) targeting effective family skills are the most cost effective for improving adolescent behavioural health. Cochrane Reviews have found the "Strengthening Families Program" (SFP) to be the most effective substance abuse prevention intervention. Standardized cultural adaptation processes resulted in successful outcomes in several countries. Objective: To promote wide-scale implementation and positive outcomes in Ireland, a unique model of inter-agency collaboration was developed plus guidelines for cultural adaptation with fidelity. Methods: 250 high-risk youth and families were recruited to complete SFP and its parent questionnaire. A quasi-experimental 2 group pre- and post-test design was employed where the norms were the comparison group. A 2 x 2 analysis of variance (ANOVA) generated the outcome tables including "p" values and Cohen's "d" effect sizes. Evaluation feedback was used to improve outcomes the next year. Results: All 21 measured outcomes had statistically significant positive results. Larger effect sizes were found for the Irish families than the USA families (d = 0.57 vs. 0.48 for youth outcomes, d = 0.73 vs. 0.65 for parenting and d = 0.76 vs. 0.70 for family outcomes). Overt and covert aggression, criminality and depression decreased more in Irish youth, but the USA youth improved more in social skills. Conclusions: This study suggests that SFP 12-16 is quite effective in reducing behavioural health problems in Irish adolescents, improving family relationships and reducing substance abuse. Additionally, the Irish interagency collaboration model is a viable solution to recruitment, retention and staffing in rural communities where finding five skilled professionals to implement SFP can be difficult.