Patient harm is a leading cause of global disease burden with considerable morbidity, mortality, and economic impacts for individuals, families, and wider society. Large bodies of evidence exist for strategies to improve safety and reduce harm. However, it is not clear which patient safety issues are being addressed globally, and which factors are the most (or least) important contributors to patient safety improvements. We aimed to explore the perspectives of international patient safety experts to identify: (1) the nature and range of patient safety issues being addressed, and (2) aspects of patient safety governance and systems that are perceived to provide value (or not) in improving patient outcomes. English-speaking Fellows and Experts of the International Society for Quality in Healthcare participated in a web-based survey and in-depth semistructured interview, discussing their experience in implementing interventions to improve patient safety. Data collection focused on understanding the elements of patient safety governance that influence outcomes. Demographic survey data were analysed descriptively. Qualitative data were coded, analysed thematically (inductive approach), and mapped deductively to the System-Theoretic Accident Model and Processes framework. Findings are presented as themes and a patient safety governance model. The study was approved by the University of South Australia Human Research Ethics Committee. Twenty-seven experts (59% female) participated. Most hailed from Africa (n = 6, 22%), Australasia, and the Middle East (n = 5, 19% each). The majority were employed in hospital settings (n = 23, 85%), and reported blended experience across healthcare improvement (89%), accreditation (76%), organizational operations (64%), and policy (60%). The number and range of patient safety issues within our sample varied widely with 14 topics being addressed. Thematically, 532 textual segments were grouped into 90 codes (n = 44 barriers, n = 46 facilitators) and used to identify and arrange key patient safety governance actors and factors as a 'system' within the System-Theoretic Accident Model and Processes framework. Four themes for improved patient safety governance were identified: (1) 'safety culture' in healthcare organizations, (2) 'policies and procedures' to investigate, implement, and demonstrate impact from patient safety initiatives, (3) 'supporting staff' to upskill and share learnings, and (4) 'patient engagement, experiences, and expectations'. For sustainable patient safety governance, experts highlighted the importance of safety culture in healthcare organizations, national patient safety policies and regulatory standards, continuing education for staff, and meaningful patient engagement approaches. Our proposed 'patient safety governance model' provides policymakers and researchers with a framework to develop data-driven patient safety policy.