Establishing a culture of safety within health care organizations requires strong leadership support. This cross-sectional survey study of nurses, allied health professionals, and unit clerks working in the inpatient setting at a single hospital found that positive perceptions of senior leadership support for safety and positive perceptions of teamwork were associated with positive perceptions of patient safety. In addition, when staff perceived senior leadership support for safety to be lacking, the positive impact of direct managerial leadership on staff perceptions of patient safety was more pronounced.