BACKGROUND: The majority of knowledge related to implementation of family-based substance use prevention programs is based on programs delivered in school and community settings. The aim of this study is to examine procedures related to implementation effectiveness and quality of two family-based universal substance use prevention programs delivered in health care settings, the Strengthening Families Program: For Parents and Youth 10-14 (SFP) and Family Matters (FM). These evidence-based programs were delivered as part of a larger random control intervention study designed to assess the influence of program choice vs. assignment on study participation and adolescent substance use outcomes. We also assess the effects of program choice (vs. assignment to program) on program delivery. METHODS: A mixed method case study was conducted to assess procedures used to maximize implementation quality and fidelity of family-based prevention programs delivered in health care settings. Families with an 11 year old child were randomly selected for study participation from health plan membership databases of 4 large urban medical centers in the San Francisco Bay Area. Eligible families were initially randomized to a Choice study condition (families choose SFP or FM) or Assigned study condition (assigned to FM, SFP or control group); 494 ethnically diverse families were selected for participation in study programs. RESULTS: Successful implementation of family prevention programs in health care settings required knowledge of the health care environment and familiarity with established procedures for developing ongoing support and collaboration. Ongoing training of program deliverers utilizing data from fidelity assessment appeared to contribute to improved program fidelity over the course of the study. Families who chose FM completed the program in a shorter period (p<.0001) and spent more time implementing program activities (p=0.02) compared to families assigned to FM. SFP "choice" families attended more sessions than those assigned to SFP (3.5 vs. 2.8), (p=0.07). CONCLUSION: Program choice appeared to increase family engagement in programs. The goals and approach of universal family-based substance use prevention programs are congruent with the aims and protocols of adolescent preventive health care services. Future effectiveness trials should assess approaches to integrate evidence-based family prevention programs with adolescent health services.