Using data from the Keystone ICU project, this study examined whether the intensive care units (ICUs) that implemented the Comprehensive Unit-based Safety Program (CUSP) would have greater improvement in safety climate, team progress barriers, and central line-associated bloodstream infections (CLABSIs) than ICUs not implementing CUSP. The study population consisted of 103 ICUs; 60 ICUs (58%) used CUSP, with 6 of them later discontinuing CUSP, and 17 ICUs (16.5%) never used CUSP. The researchers could not determine CUSP use status for the remaining 26 ICUs because of missing data. The use of CUSP was associated with improved safety climate, job satisfaction, and working conditions after a 2-year period, as measured by the Safety Attitudes Questionnaire. Study results on barriers and CLABSIs are inconclusive. This study demonstrated that unit-based, formalized processes targeting cultural improvements in teamwork, communication, self-identification of hazards, and hazard mitigation can improve several aspects of patient safety climate in ICUs.