Introduction: Proton pump inhibitors (PPIs) are effective treatments for upper gastrointestinal pathologies and short-term courses are well-tolerated. However, indiscriminate use of PPIs is undesirable due to its potential harms. We implemented a series of deprescribing interventions between 2016 and 2017 to curb PPI overutilisation in our institution. The aim of this study was to evaluate the effectiveness and safety of these interventions. Methods: An institutional PPI deprescribing guide was disseminated by email and educational roadshows were conducted to prescribers. Interrupted time series analysis was used to evaluate the effectiveness of the deprescribing interventions over a 7-year period from 2013 to 2019. To ascertain the safety of PPI deprescribing, we analysed the peptic ulcer disease incidence from 2015 to 2018 and conducted a retrospective chart review of 262 inpatients who were deprescribed PPIs. Results: Following the first intervention, there was a significant decrease in mean oral PPI utilisation by 2,324.46 defined daily doses (DDD) per 1,000 prescriptions (95% confidence interval [CI] -3,542.66, -1,106.26) per month, followed by a month-to-month decrease of 302.61 DDD per 1,000 prescriptions per month thereafter (95% CI -473.95, -131.27). A second targeted educational intervention was only effective in sustaining the decline in the outpatient, but not in the inpatient setting. There were no significant changes in incidence of peptic ulcer disease. In the retrospective chart review, a majority (62.6%) of patients remained deprescribed at 6 months. Conclusion: We observed a sustained decrease in PPI utilisation in our institution for more than 12 months following our educational interventions. Cautious deprescribing of PPIs in eligible candidates was found to be safe with low recurrence rates of upper gastrointestinal events. Keywords: Deprescribing, drug utilisation study, interrupted time series analysis, proton pump inhibitor, quality improvement initiative