BACKGROUND: Falls in older patients can lead to serious health complications and increased health care costs. Fall risk-increasing drugs (FRIDs) are a group of drugs that may induce falls or increase the tendency to fall (ie, fall risk). Deprescribing is the process of withdrawal from an inappropriate medication, supervised by a health care professional, with the goal of managing polypharmacy and improving outcomes. OBJECTIVE: This study aims to assess the effectiveness of a deprescribing intervention based on the Assess, Review, Minimize, Optimize, and Reassess (ARMOR) tool in reducing the risk of falls in older patients and evaluate the cost-effectiveness of deprescribing FRIDs. METHODS: This is an open-label, parallel-group randomized controlled academic trial. Individuals aged 60-80 years who are currently taking 5 or more prescribed drugs, including at least 1 FRID, will be recruited. Demographic data, medical conditions, medication lists, orthostatic hypotension, and fall history details will be collected. Fall concern will be assessed using the Fall Efficacy Scale, and fall risk will be assessed by the Timed Up and Go test and Tinetti Performance-Oriented Mobility Assessment tool. In this study, all treating physicians will be randomized using a stratified randomization method based on seniority. Randomized physicians will do deprescribing with the ARMOR tool for patients on FRIDs. Participants will maintain diaries, and monthly phone follow-ups will be undertaken to monitor falls and adverse events. Physical assessments will be performed to evaluate fall risk every 3 months for a year. The rationality of prescription drugs will be evaluated using the World Health Organization's core indicators. RESULTS: The study received a grant from the Indian Council of Medical Research-Safe and Rational Use of Medicine in October 2023. The study is scheduled to commence in April 2024 and conclude by 2026. Efficacy will be measured by fall frequency and changes in fall risk scores. Cost-effectiveness analysis will also include the incremental cost-effectiveness ratio calculation. Adverse events related to deprescription will be recorded. CONCLUSIONS: This trial will provide essential insights into the efficacy of the ARMOR tool in reducing falls among the geriatric population who are taking FRIDs. Additionally, it will provide valuable information on the cost-effectiveness of deprescribing practices, offering significant implications for improving the well-being of older patients and optimizing health care resource allocation. The findings from this study will be pertinent for health care professionals, policy makers, and researchers focused on geriatric care and fall prevention strategies. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2023/12/060516; https://ctri.nic.in/Clinicaltrials/pubview2.php. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55638.