Background: Delirium is an acute change in mental status affecting 10%-64% of hospitalized patients, and may be preventable in 30%-40% of cases. In October 2013, a task force for delirium prevention and early identification in medical-surgical units was formed at our hospital. We studied whether our standardized protocol prevented delirium among high-risk patients., Methods: We studied 105,455 patient encounters between November 2013 and January 2018. Since November 2013, there has been ongoing education to decrease deliriogenic medications use. Since 2014, nurses screen all patients for presence or absence of delirium using the Confusion Assessment Method (CAM). Since 2015, nurses additionally screen all patients for risk of delirium. In 2015, a physician order set for delirium was created. Nonpharmacological measures are implemented for high-risk or CAM positive patients., Results: 98.8% of patient encounters had CAM screening, and 99.6% had delirium risk screening. Since 2013, odds of opiate use decreased by 5.0% per year (P < .001), and odds of benzodiazepine use decreased by 8.0% per year (P < .001). There was no change in anticholinergic use. In the adjusted analysis, since 2015, odds of delirium decreased by 25.3% per year among high-risk patients (n = 21,465; P < .001). Among high-risk patients or those diagnosed with delirium (n = 22,121), estimated length of stay decreased by 0.13 days per year (P < .001), odds of inpatient mortality decreased by 16.0% per year (P = .011), and odds of discharge to a nursing home decreased by 17.1% per year (P < .001)., Conclusion: With high clinician engagement and simplified workflows, our delirium initiative has shown sustained results., (Copyright © 2019 Elsevier Inc. All rights reserved.)