Patient safety culture has a positive influence on the effectiveness of patient safety and quality improvement interventions. A study was conducted to gain knowledge about promising best practices used by hospitals to improve patient safety culture hospitalwide. Agency for Healthcare Research and Quality (AHRQ) Surveys on Patient Safety Culture™ (SOPS) Hospital Survey longitudinal results from 536 hospitals that submitted data to the Hospital SOPS database from 2007 to 2014 were analyzed. Composite-level and aggregate improvement was measured, resulting in the identification of "top-improving," large hospitals (400 + beds). Semistructured interviews were conducted with one to three interviewees (for example, Vice President of Clinical Quality, Patient Safety Officer, Chief Medical Officer) from six top-improving hospitals. The transcripts of the interviews were analyzed to identify common themes and best practices among the hospitals. The mean change in the all-composite percent positive culture score was a 1.7 percentage point increase. The six hospitals interviewed had an average increase of 8.6 percentage points (range, 6.5-10.6) in their culture score. The three most common practices for improving culture as described by the hospital quality leaders from the six hospitals were (1) goal setting and strong action planning for quality improvement, (2) implementation of well-known patient safety initiatives and programs, and (3) rigorous survey administration methods. Among six large hospitals that improved their hospitalwide culture score, the common best practices were the implementation of routine culture measurement with a wide dissemination of results, strong action planning for improvement that includes leadership support and involvement from all staff levels, and multifaceted patient safety programs and education.