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The IOM identified patient safety as a significant problem. This paper describes the implementation and validation of a comprehensive unit-based safety program (CUSP) in intensive care settings.An 8-step safety program was implemented in the Weinberg ICU, with a second control (SICU) subsequently receiving the intervention. Unit improvement teams (physician, nurse, administrator) were identified to champion efforts between staff and Safety Committee. CUSP steps: (1) culture of safety assessment; (2) sciences of safety education; (3) staff identification of safety concerns; (4) senior executives adopt a unit; (5) improvements implemented from safety concerns; (6) efforts documented/analyzed; (7) results shared; and (8) culture reassessment.Safety culture improved post versus pre-intervention (35% to 52% in WICU and 35% to 67% in SICU). Senior executive adoption led to patient transport teams and pharmacy presence in ICUs. Interventions from safety assessment included: medication reconciliation, short-term goals sheet and relabeling epidural catheters. One-year post-CUSP implementation, length of stay (LOS) decreased from 2 to 1 day in WICU and 3 to 2 days in SICU (P < 0.05 WICU and SICU). Medication errors in transfer orders were nearly eliminated, and nursing turnover decreased from 9% to 2% in WICU and 8% to 2% in SICU (neither statistically significant).CUSP successfully implemented in 2 ICUs. CUSP can improve patient safety and reduce medication errors, LOS, and potentially nursing turnover.