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Patient safety is a significant problem and one that merits further attention. Errors are underreported, handoffs are inadequate, and central line-associated bloodstream infections (CLABSIs) continue to occur unnecessarily. As many as 70 percent of medical errors result from poor patient handoffs. Underreporting of these adverse events may be as high as 96 percent. Furthermore, a conservative estimate puts annual deaths from CLABSIs at 31,000. The objective of this three-study dissertation was to identify perceived organizational factors of safety associated with a high frequency of error reporting, successful handoffs, and lower CLABSI rates. The error reporting and handoff studies aimed to find an organizational factor that had the highest association with that outcome. Those studies also assessed differences in perceptions between management and clinical staff, as well as between different clinical staff groups. The CLABSI study sought to identify the organizational factors of safety associated with reduced CLABSI rates. Another goal of that study was to try to identify the hospital units most likely to achieve zero CLABSIs after implementation of the Comprehensive Unit Based Safety (CUSP) methodology.The Hospital Survey on Patient Safety Culture (HSOPS) was analyzed in conjunction with data on CLABSIs from On the CUSP: Stop BSI program funded by the Agency for Healthcare Research and Quality (AHRQ). The data set for the handoff and error reporting studies consisted of 515,637 respondents in 1,052 hospitals. It was analyzed using weighted least squares multiple regressions. Poisson, and logistic regressions were used for the CLABSI study of 438 hospitals.Management support for safety, error feedback, and organizational learning were all significantly associated with error reporting. Feedback on error reports had the most significant association with error reporting. Management support for safety was not a significant predictor of error reporting for managers, but it was for physicians and nurses. In the second study, management support, teamwork across units, and staffing were all significant predictors of successful handoffs. Teamwork across units similarly had the greatest positive perceived impact on patient handoffs. There was a significant difference in perceptions between management and clinical staff regarding organizational learning, or continuous improvement activities. In the third study, CLABSI rates decreased significantly following the introduction of the CUSP program. Hospitals should prioritize introduction of CUSP to units that have better perceived staffing and teamwork across units since these organizational factors were associated with zero CLABSIs after CUSP implementation. Once CUSP is introduced on a unit, hospital leadership needs to support patient safety, and ensure there are strong mechanisms for reflective activities, such as organizational learning and error feedback.To summarize all three studies, improvements in organizational factors of safety are positively linked to safety outcomes. Management support for safety, teamwork across units, and organizational learning had a positive effect in all three studies, thus demonstrating their consistent influence on patient safety. Furthermore, there was support for the conceptual model that enabling, enacting, and elaborating actions impact patient safety outcomes.