BACKGROUND:There is widespread recognition that creating a safety culture supports high-quality health care. However, the complex factors affecting cultural change interventions are not well understood. This study examines factors influencing the implementation of an intervention to promote professionalism and build a safety culture at an Australian hospital. METHODS:The study was completed midway into the three-year intervention and involved collecting qualitative data from two sources. First, face-to-face interviews were conducted pre- and mid-intervention with a purposely selected sample. Second, a survey with three open-ended questions was completed one year into the intervention by clinical and patient support staff. Data from interviews and survey questions were analyzed using a combination of inductive and deductive approaches. RESULTS:A total of 25 participants completed preintervention interviews, and 24 took part mid-intervention. Of the 2,047 staff who completed the survey (61% response rate), 59.1% of respondents answered at least one open-ended question. Multiple interrelated factors were identified as enhancing intervention implementation. These include sustaining a favorable implementation climate, leaders consistently demonstrating behaviors that support a safety culture, increasing compatibility of working conditions with intervention aims, building confidence in systems to address unprofessional behaviors, and responding to evolving needs. CONCLUSION:Strengthening safety culture remains an enduring challenge, but this study yields valuable insights into factors influencing implementation of a multifaceted behavior change intervention. The findings provide a basis for practical strategies that health care leaders seeking cultural improvements can employ to enhance the delivery of similar interventions and address potential impediments to success.