Background: Safety net hospitals, which serve vulnerable and underserved populations and often operate on smaller budgets than non-safety net hospitals, may experience unique implementation challenges. We sought to describe common barriers and facilitators that affect the implementation of improvement initiatives in a safety net hospital, and identify potentially transferable lessons to enhance implementation efforts in similar settings. Methods: We interviewed leaders within five inpatient departments and asked them to identify the priority inpatient improvement initiative from the last year. We then conducted individual, semi-structured interviews with 25 stakeholders across the five settings. Interviewees included individuals serving in implementation oversight, champion, and frontline implementer roles. The Consolidated Framework for Implementation Research informed the discussion guide and a priori codes for directed content analysis. Results: Despite pursuing diverse initiatives in different clinical departments, safety net hospital improvement stakeholders described common barriers and facilitators related to inner and outer setting dynamics, characteristics of individuals involved, and implementation processes. Implementation barriers included (1) limited staffing resources, (2) organizational recognition without financial investment, and (3) the use of implementation strategies that did not adequately address patients' biopsychosocial complexities. Facilitators included (1) implementation approaches that combined passive and active communication styles, (2) knowledge of patient needs and competitive pressure to perform well against non-SNHs, (3) stakeholders' personal commitment to reduce health inequities, and (4) the use of multidisciplinary task forces to drive implementation activities. Conclusion: Inner and outer setting dynamics, individual's characteristics, and process factors served as implementation barriers and facilitators within the safety net. Future work should seek to leverage findings from this study toward efforts to enact positive change within safety net hospitals.