More than 20 million people in the United States have a substance use disorder, resulting in negative individual and societal outcomes. An evidence-based intervention, Screening, Brief Intervention, and Referral to Treatment (SBIRT), involves screening patients to assess for substance use and then providing a brief intervention and referral to treatment when indicated. This evidence-based intervention is underutilized in healthcare settings. The purpose of this dissertation was to contribute to the body of evidence regarding the implementation of SBIRT in healthcare settings. Specifically, the aims of this dissertation were to 1) provide an overview of the evidence regarding the use of implementation strategies to facilitate the implementation of SBIRT, 2) describe implementation of SBIRT by nurses in acute care hospitals, and 3) examine individual and organizational characteristics associated with the intra-organizational adoption of SBIRT. To review the literature, a scoping review was completed on 18 articles that met the inclusion criteria. The review found that leaders often train and educate stakeholders to facilitate the implementation of SBIRT, but less attention has been given to adapting the intervention or engaging patients. Additionally, implementation efforts led to increases in screening, but the evidence regarding the effect on brief intervention is inconclusive, and evidence regarding referral to treatment is scarce. Eighteen nurses participated in a qualitative descriptive study of the implementation of SBIRT, and data were analyzed using content analysis. Participants identified barriers and facilitators associated with the nurses' attitudes and beliefs about SBIRT, organizational factors, and patients' response to the SBIRT process. Participants indicated that SBIRT was a useful intervention that was best implemented by providing a clear process and incorporating SBIRT into an established workflow. To examine factors related to intra-organizational adoption of a tool to screen patients for substance use, two hundred twenty-two nurses participated in a crosssectional study. Results of this study indicate that training and the perception of peer usage of the intervention were significantly related to individual nurses' use of the intervention in practice. The findings of this dissertation can inform research and practice regarding the implementation of SBIRT in healthcare settings.