Background: Unhealthy alcohol use includes the spectrum of alcohol consumption from risky drinking to alcohol use disorders. Routine alcohol screening, brief intervention (BI) and referral to treatment (RT) are commonly endorsed for improving the identification and management of unhealthy alcohol use in outpatient settings. However, factors which might impact screening, BI, and RT implementation in inpatient settings, particularly if delivered by nurses, are unknown, and must be identified to effectively plan randomized controlled trials (RCTs) of nurse-delivered BI. The purpose of this study was to identify the potential barriers and facilitators associated with nurse-delivered alcohol screening, BI and RT for hospitalized patients., Methods: We conducted audio-recorded focus groups with nurses from three medical-surgical units at a large urban Veterans Affairs Medical Center. Transcripts were analyzed using modified grounded theory techniques to identify key themes regarding anticipated barriers and facilitators to nurse-delivered screening, BI and RT in the inpatient setting., Results: A total of 33 medical-surgical nurses (97% female, 83% white) participated in one of seven focus groups. Nurses consistently anticipated the following barriers to nurse-delivered screening, BI, and RT for hospitalized patients: (1) lack of alcohol-related knowledge and skills; (2) limited interdisciplinary collaboration and communication around alcohol-related care; (3) inadequate alcohol assessment protocols and poor integration with the electronic medical record; (4) concerns about negative patient reaction and limited patient motivation to address alcohol use; (5) questionable compatibility of screening, BI and RT with the acute care paradigm and nursing role; and (6) logistical issues (e.g., lack of time/privacy). Suggested facilitators of nurse-delivered screening, BI, and RT focused on provider- and system-level factors related to: (1) improved provider knowledge, skills, communication, and collaboration; (2) expanded processes of care and nursing roles; and (3) enhanced electronic medical record features., Conclusions: RCTs of nurse-delivered alcohol BI for hospitalized patients should include consideration of the following elements: comprehensive provider education on alcohol screening, BI and RT; record-keeping systems which efficiently document and plan alcohol-related care; a hybrid model of implementation featuring active roles for interdisciplinary generalists and specialists; and ongoing partnerships to facilitate generation of additional evidence for BI efficacy in hospitalized patients.