Patient safety continues to be a serious health concern in acute-care hospitals. Safety culture has been a frequent target for patient safety improvement over the past decade, based on recommendations from the Institute of Medicine and its use in industry. However, the relationship between safety culture and patient safety in acute-care hospitals has yet to be systematically examined. Thus, a meta-analysis was devised to examine the relationship between patient safety outcomes and safety culture in that setting. Due to the limited empirical research reports available, five small pilot meta-analyses were conducted, examining the relationship between safety culture and each of the following: pressure ulcers, falls, medication errors, nurse-sensitive outcomes, and post-operative outcomes. No significant relationships of any size were identified. An assessment of the relevant literature is presented, offering potential explanations for this surprising finding and an agenda for future research.