Objectives: To map the randomized trial evidence describing the feasibility of discontinuing active medications with potential adverse effects in older patients. Design: Scoping review with systematic search of PubMed, Embase, and Cochrane Library. Setting and Participants: Randomized trials investigating discontinuation of a single medicine or medicine class in patients with mean age ≥65 years. Methods: We extracted trial characteristics including study design and assessed bias. As proxies for the “feasibility of discontinuation,” we extracted the “dropout rate” and “disease recurrence rate.” Results: We identified 40 trials investigating discontinuation of symptomatic (n = 26), preventive (n = 6), or both preventive and symptomatic medicines (n = 8) against psychiatric (n = 10), neurologic (n = 9), musculoskeletal (n = 8), cardiovascular (n = 5), respiratory (n = 4), and urologic diseases (n = 4). Five discontinuation designs were used, 75% (30/40) of trials were placebo-controlled, and 48% (19/40) of trials had bias disfavoring discontinuation. The dropout rate was similar between the discontinuation group and the continuation group in 79% of the trials (30/38), whereas disease recurrence was similar in 72% (23/32) of the trials. In 42% (13/31) of trials reporting both dropout rate and disease recurrence rate, the differences between groups were statistically insignificant and less than 10%; these trials investigated discontinuation of cholinesterase inhibitors for Alzheimer's disease in various settings (n = 3), alendronate for osteoporosis (n = 3), glucosamine for osteoarthritis, lithium as adjunct for unipolar depression, statins for cardiovascular disease in patients with limited life expectancy, droxidopa for neurogenic orthostatic hypotension, tamsulosin for lower urinary tract symptoms, sertraline for major depressive episode, and fentanyl patch for low back or osteoarthritis pain. Conclusions and Implications: We identified 40 randomized trials using a variety of designs investigating discontinuation of both symptomatic and preventive medicines in older patients. Discontinuation of medicines seems feasible for most of the investigated medicines. This scoping review can guide clinical practice and future trials on deprescribing.