This article describes a limited statewide dissemination of an evidence-based technology, screening, brief intervention, and referral to treatment (SBIRT), and evaluation of the effects on emergency department (ED) systems of care, utilizing the knowledge translation framework of reach, effectiveness, adoption, implementation, and maintenance (RE-AIM), using both quantitative and qualitative data sources. Screening and brief intervention (SBI) can detect high-risk and dependent alcohol and drug use in the medical setting, provide early intervention, facilitate access to specialty treatment when appropriate, and improve quality of care. Several meta-analyses demonstrate its effectiveness in primary care, and the federal government has developed a well-funded campaign to promote physician training and adoption of SBI. In the busy environment of the ED, with its competing priorities, researchers have tested a collaborative approach that relies on peer educators, with substance abuse treatment experience and broad community contact, as physician extenders. The ED-SBIRT model of care reflects clinician staff time constraints and resource limitations and is designed for the high rates of prevalence and increased acuity typical of ED patients. This report tracks services provided during dissemination of the ED-SBIRT extender model to seven EDs across a northeastern state, in urban, suburban, and rural community settings. Twelve health promotion advocates (HPAs) were hired, trained, and integrated into seven ED teams. Over an 18-month start-up period, HPAs screened 15,383 patients; of those, 4,899 were positive for high risk or dependent drinking and/or drug use. Among the positive screens, 4,035 (82%) received a brief intervention, and 57% of all positives were referred to the substance abuse treatment system and other community resources. Standardized, confidential interviews were conducted by two interviewers external to the program with 24 informants, including HPAs and their supervisors, clinicians, nurse managers, and ED directors across five sites. A detailed semistructured format was followed, and results were coded for thematic material. Barriers, challenges, and successes are described in the respondents' own words to convey their experience of this demonstration of SBIRT knowledge translation. Five of seven sites were sustained through the second year of the program, despite cutbacks in state funding. The dissemination process provided a number of important lessons for a large rollout. Successful implementation of the ED-SBIRT HPA model depends on 1) external funding for start-up; 2) local ED staff acting as champions to support the HPA role, resolve territorial issues, and promote a cultural shift in the ED treatment of drug and alcohol misuse from "treat and street" to prevention, based on a knowledge of the science of addiction; 3) sustainability planning from the beginning involving administrators, the billing and information technology departments, medical records coders, community service providers, and government agencies; and 4) creation and maintenance of a robust referral network to facilitate patient acceptance and access to substance abuse services.