Stress ulcer prophylaxis (SUP) with acid suppressive therapy is often inappropriately prescribed in the intensive care setting. Acid suppressive therapy, including proton pump inhibitors and histamine-2 receptor antagonists, has been associated with adverse effects, including increased risk of nosocomial infections. Reduction in the rate of inappropriate use of SUP may mitigate the risk of medication adverse effects and unnecessary health care costs. Our interdisciplinary team executed a bundled quality improvement initiative to reduce inappropriate use of SUP in the ICU, which included ( a) developing evidence-based clinical practice guidelines for use of SUP, ( b) implementing these clinical guidelines with an education intervention targeting ICU health care providers, and ( c) determining provider attitudes regarding SUP use before and after implementation of the bundled initiative. Within 1 month following implementation, inappropriate SUP (per patient hospital day) decreased from 19% to 6.6% ( P = .002). Our multidisciplinary bundled quality improvement initiative reduced inappropriate use of SUP. The program was successfully integrated into the pharmacists’ workflow, thus yielding a sustainable impact on SUP use.