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Treatment of nontraumatic shock is often delayed or inadequate due to insufficient knowledge or skills of front-line healthcare providers, limited hospital resources, and lack of institution-wide systems to ensure application of best practice. As a result, mortality from shock remains high. We designed a study to determine whether outcomes will be improved by a hospital-wide system that educates and empowers clinicians to rapidly identify and treat patients in shock with a multidisciplinary team using evidenced-based protocols.Single-center trial before and after implementation of a hospital-wide rapid response system for early identification and treatment of patients in shock.A 180-bed regional referral center in northern California.A total of 511 adult patients who met criteria for shock during a 7-yr period.We designed a rapid response system that included a comprehensive educational program for clinicians on earlier recognition of shock, empowerment of front-line providers using specific criteria to initiate therapy, mobilization of the rapid response team, protocol goal-directed therapy, and early transfer to the intensive care unit. Outcome feedback was provided to foster adoption.We measured times to key interventions and hospital mortality 2.5 yrs before and until 5 yrs after system initiation. Times to interventions and mortality decreased significantly over time before and after adjusting for confounding factors. Interventions times, including shock alert activation, infusion of 2 L of fluid, central venous catheter placement, and antibiotic administration, were significant predictors of mortality (p < .05). Overall and septic subgroup mortality decreased from before system implementation through protocol year 5 from 40% to 11.8% and from 50% to 10%, respectively (p < .001).Over time, a rapid response system for patients in shock continued to reduce time to treatment, resulting in a continued decrease in mortality. By year 5, only three patients needed to be treated to save one additional life.