Large-scale (e.g., national) programs could strengthen safety culture, which is foundational to patient safety, yet we know little about how to optimize this potential. In 2013, Brazil’s Ministry of Health launched the National Patient Safety Program, involving hospital-level safety teams and targeted safety protocols. We conducted in-depth qualitative case studies of National Patient Safety Program implementation in two hospitals, with different readiness, to understand how program implementation affected enabling, enacting, and elaborating processes that produce and sustain safety culture. For both hospitals, external mandates were insufficient for enabling hospital-level action. Internal enabling failures (e.g., little safety-relevant senior leadership) hindered enactment (e.g., safety teams unable to institute plans). Limited enactment and weak elaboration processes (e.g., bureaucratic monitoring) failed to institutionalize protocol use and undermined safety culture. Optimizing the safety culture impact of large-scale programs requires effective multi-level enabling and capitalizing on the productive potential of interacting national- and local-level influences.
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