BACKGROUND:Screening, brief intervention, and referral to treatment (SBIRT) for substance use has an impact on morbidity and mortality and health care cost. LOCAL PROBLEM:Nurses in ambulatory care settings may lack knowledge about evidence-based substance use SBIRT. METHODS:A comparison of pre- and postintervention data was performed to determine whether knowledge improved and to identify facilitators and barriers to SBIRT implementation. INTERVENTIONS:Nurses completed an online self-paced program focusing on alcohol and drug use screening, motivational interviewing used in a brief intervention, and referral to specialty treatment. RESULTS:Postintervention knowledge scores increased (P < .001). Facilitator and barrier themes included time, education, resources, receptivity, and interprofessional collaboration. CONCLUSIONS:The implementation of the SBIRT online program was feasible for nurses to complete during work hours and resulted in increased SBIRT-related knowledge.