•Health care-associated infections are an important public health and patient safety issue.•A bundle is a specific tool with clear parameters to guide the multidisciplinary team in the intensive care unit.•Central line-associated blood stream infection, catheter-associated urinary tract infection, and ventilator-associated pneumonia rates declined 58.6%, 56.7%, and 82.6%, respectively, after bundle implementation. A retrospective cohort study was conducted to evaluate the bundle of techniques developed by the multidisciplinary team to minimize infections in an adult intensive care unit over a 22-year span. Two periods were analyzed: 1996-2006 and 2007-2017. Bloodstream infections, urinary tract infections, and ventilator-associated pneumonia declined 58.6%, 56.7%, and 82.6%, respectively (P < .05) from 2007 to 2017 compared with these same infections during 1996-2006.