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To evaluate the impact of a comprehensive unit-based safety program on safety climate in a large cohort of intensive care units participating in the Keystone intensive care unit project.A prospective cohort collaborative study to improve quality of care and safety culture by implementing and evaluating patient safety interventions in intensive care units predominantly in the state of Michigan.The comprehensive unit-based safety program was the first intervention implemented by every intensive care unit participating in the collaborative. It is specifically designed to improve the various elements of a unit's safety culture, such as teamwork and safety climate. We administered the validated Safety Attitudes Questionnaire at baseline (2004) and after 2 yrs of exposure to the safety program (2006) to assess improvement. The safety climate domain on the survey includes seven items.Post-safety climate scores for intensive care units. To interpret results, a score of <60% was in the “needs improvement” zone and a ≥10-point discrepancy in pre-post scores was needed to describe a difference. Hospital bed size, teaching status, and faith-based status were included in our analyses. Seventy-one intensive care units returned surveys in 2004 and 2006 with 71% and 73% response rates, respectively. Overall mean safety climate scores significantly improved from 42.5% (2004) to 52.2% (2006), t = −6.21, p < .001, with scores higher in faith-based intensive care units and smaller-bed-size hospitals. In 2004, 87% of intensive care units were in the “needs improvement” range and in 2006, 47% were in this range or did not score ≥10 points or higher. Five of seven safety climate items significantly improved from 2004 to 2006.A patient safety program designed to improve teamwork and culture was associated with significant improvements in overall mean safety climate scores in a large cohort of 71 intensive care units. Research linking improved climate scores and clinical outcomes is a critical next step.