Patient safety experts identify changes in culture as critical to creating safer care (Flin, 2007; Leape, 1994; Reason, 1997; Vincent, Taylor-Adams & Stanhope, 1998). Yet there is limited understanding of how to best study, evaluate and make changes to patient safety culture. The literature on organizational culture, safety sciences and health services research suggests varying perspectives on studying culture and an evolving approach to creating tools to measure culture change. This thesis reports two projects. The first project used the Manchester Patient Safety Culture Assessment Tool, the Modified Stanford Instrument, and qualitative interviews to examine whether safety culture profiles varied by research method and instrument used to assess culture. Comparative assessment of the results suggests that while the quantitative measurement tools provide a high level organizational summary of safety issues, the qualitative interviews provide a more fine-grained understanding of the contextual and local features of the culture. The second research project used a multiple case study design to understand what hospitals have learned from trying to improve patient safety culture. Interviews in three organizations were used to determine how these organizations shifted their cultures. Although each organization had different experiences and used varying methods, they all created culture change through the simultaneous implementation of practice, policies and strategic framing of patient safety culture concepts in their everyday work. The third research paper examined how leaders measured changes in patient safety culture. Both leaders and front line workers look to both process measures (e.g., talking about safety and encouraging patient safety activities) together with outcome measures (e.g., adverse events, infection rates, and culture survey results) to evaluate their success in culture change. Overall this dissertation deepens our knowledge of how methods influence our assessment of patient safety culture and how leaders influence culture change. Future research needs to assess in more detail the roles of leaders and middle managers to understand how these individuals are able to reconcile the practice environment challenges while continuing to create a culture of patient safety.