Background: Quality and safety improvement programmes advance the standard of care delivered by health organisations but have been shown to be less effective than anticipated. Implementing improvement programmes require a greater understanding of the impact of the social context and strategies that engage staff. Objective: To investigate factors that shaped the development of interprofessional improvement initiatives in a health organisation. Methods: Data are drawn from a large-scale longitudinal action research study examining interprofessional learning and practice. The setting is an autonomous bounded health jurisdiction in Australia. Within the study, health professionals have conceptualised more than 111 interprofessional improvement projects, of which 76 have evolved into ongoing activities. Textual data were analysed using emergent coding and descriptive statistics. Results: Initiatives were shaped by six determinants: site receptivity; team issues; leadership; impact on healthcare relations; impact on quality and safety issues; and extent to which the projects became institutionally embedded. Initiatives that engaged participants and progressed were characterised by and displayed flexible leadership, and ongoing refinement and maturity over time. The local organisational context and initiatives coevolved. Conclusions: Improvement initiatives are necessary for improved quality of care and patient safety but are difficult to implement and sustain. The factors identified to develop them are constantly under challenge in health services. Improving healthcare quality will, in part, depend upon the ability to provide more flexible and supportive social contexts.