INTRODUCTION: Implementation of the Drug Burden Index (DBI) as a risk assessment tool in clinical practice may facilitate deprescribing. OBJECTIVE: The purpose of this study is to evaluate how a comprehensive intervention bundle using the DBI impacts (i) the proportion of older inpatients with at least one DBI-contributing medication stopped or dose reduced on discharge, compared with admission; and (ii) the changes in deprescribing of different DBI-contributing medication classes during hospitalisation. METHODS: This before-and-after study was conducted in an Australian metropolitan tertiary referral hospital. Patients aged ≥ 75 years admitted to the acute aged care service for ≥ 48 h from December 2020 to October 2021 and prescribed DBI-contributing medication were included. During the control period, usual care was provided. During the intervention, access to the intervention bundle was added, including a clinician interface displaying DBI score in the electronic medical record. In a subsequent 'stewardship' period, a stewardship pharmacist used the bundle to provide clinicians with patient-specific recommendations on deprescribing of DBI-contributing medications. RESULTS: Overall, 457 hospitalisations were included. The proportion of patients with at least one DBI-contributing medication stopped/reduced on discharge increased from 29.9% (control period) to 37.5% [intervention; adjusted risk difference (aRD) 6.5%, 95% confidence intervals (CI) -3.2 to 17.5%] and 43.1% (stewardship; aRD 12.1%, 95% CI 1.0-24.0%). The proportion of opioid prescriptions stopped/reduced rose from 17.9% during control to 45.7% during stewardship (p = 0.04). CONCLUSION: Integrating a comprehensive intervention bundle and accompanying stewardship program is a promising strategy to facilitate deprescribing of sedative and anticholinergic medications in older inpatients.