Understanding how safety culture mechanisms affect nursing safety-oriented behavior and thus patient outcomes is critical to developing hospital safety programs. Safety priming refers to communicating safety values intended to activate patient safety goals. Safety priming through nursing handoff communication was tested as a means by which cultural safety values may affect nursing practice. The mixed-methods pilot study setting was an academic medical center’s high-fidelity simulation lab. Twenty nurses were randomized into intervention and control groups. The intervention group received a safety priming intervention; all participants were observed for completing appropriate actions in response to patient safety risks embedded in a scenario. Stimulated recall interviews were conducted following simulation completion. Nurses receiving the safety priming intervention performed slightly but non-significantly more safety actions than nurses who did not (60.5% vs. 57.9% of 43 actions). Implications for both research and practice are discussed for interventions targeting routine versus safety goal-directed nursing actions.