The Surviving Sepsis Campaign (SSC) developed guidelines for managing severe sepsis and septic shock, aiming to improve clinical outcomes. A performance improvement initiative was launched to change clinical behavior through bundles based on key SSC guidelines. The initiative was implemented voluntarily in hospitals and regional networks across the US, Europe, and South America. Data from 15,022 patients at 165 sites were analyzed over a 2-year period. Compliance with the resuscitation bundle increased from 10.9% to 31.3%, and with the management bundle from 18.4% to 36.1%. Unadjusted hospital mortality decreased from 37% to 30.8%. Adjusted odds ratios showed a significant reduction in mortality over time, with an absolute drop of 0.8% per quarter and 5.4% over 2 years. The study demonstrates that a multifaceted performance improvement initiative can lead to sustained quality improvement in sepsis care, with a reduction in hospital mortality rates.The Surviving Sepsis Campaign (SSC) developed guidelines for managing severe sepsis and septic shock, aiming to improve clinical outcomes. A performance improvement initiative was launched to change clinical behavior through bundles based on key SSC guidelines. The initiative was implemented voluntarily in hospitals and regional networks across the US, Europe, and South America. Data from 15,022 patients at 165 sites were analyzed over a 2-year period. Compliance with the resuscitation bundle increased from 10.9% to 31.3%, and with the management bundle from 18.4% to 36.1%. Unadjusted hospital mortality decreased from 37% to 30.8%. Adjusted odds ratios showed a significant reduction in mortality over time, with an absolute drop of 0.8% per quarter and 5.4% over 2 years. The study demonstrates that a multifaceted performance improvement initiative can lead to sustained quality improvement in sepsis care, with a reduction in hospital mortality rates.