The authors' goal was to determine if a national intensive care unit (ICU) collaborative to reduce central line-associated bloodstream infections (CLABSIs) would succeed in Hawaii. The intervention period (July 2009 to December 2010) included a comprehensive unit-based safety program; a multifaceted approach to CLABSI prevention; and monitoring of infections. The primary outcome was CLABSI rate. A total of 20 ICUs, representing 16 hospitals and 61 665 catheter days, were analyzed. Median hospital bed size was 159 (interquartile range [IQR] = 71-212) and median ICU bed size was 10 (IQR = 8-12). Median unit catheter days per month were 112 (IQR = 52-197). The overall mean CLABSI rate decreased from 1.5 infections per 1000 catheter days at baseline (January to June 2009) to 0.6 at 16 to 18 months postintervention (October to December 2010). The median rate was zero CLABSIs per 1000 catheter days at baseline and remained zero throughout the study period. Hawaii demonstrated that the national program can be successfully spread, providing further evidence that most CLABSIs are preventable.