Aims: To describe the medication changes implemented during physician-led medication reviews that resulted in improved health-related quality of life; and to explore factors that could identify patients with overprescription.Methods: Post-hoc analyses of data from a pragmatic, non-blinded, randomized clinical trial investigating a medication review intervention (NCT03911934) in 408 geriatric outpatients taking \(\geq\)9 medicines.Results: The most frequent medicine change in the medication review group (n=196) was discontinuation (26% of the medicines) due to lack of indication (72% of the discontinuations). After 13 months, 82% of the discontinued medicines were persistently discontinued. The medicines most often discontinued in the medication review group compared with usual care included: metoclopramide (11/5=73% discontinued vs 1/12=8% in usual care), acetylsalicylic acid (20/48=42% vs 2/47=4%), simvastatin (18/48=38% vs 2/58=3%), zopiclone (23/59=39% vs 4/54=7%), quinine (9/14=64% vs 6/16=38%), citalopram (4/18=22% vs 0/20=0%), and tramadol (18/37=49% vs 8/30=27%). Factors associated with the number of overprescribed medicines included: number of prescribed medicines (8% increase per medicine), Drug Burden Index (15% increase per 1 increase), and patient motivation for medicine changes (26% less if not motivated). Prescriptions of metoclopramide, iron preparations, antidepressants other than SSRIs, NSAIDs, or drugs for urinary incontinence were associated with a higher number of overprescribed medicines.Conclusion: Medication reviews can be used to persistently discontinue overprescribed medicines in older polypharmacy patients. Motivation for having their medicine changed, treatment with a higher number of medicines, and a higher burden of sedative and anticholinergic drugs characterized patients most likely to benefit from physician-led medication reviews.