Background: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. Methods: Design: systematic review and meta-analysis. Data sources: Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. Eligibility criteria: randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. Study records: title/abstract and full-text screening by two reviewers. Risk of bias: Cochrane Collaboration revised tool. Data synthesis: results reported separately for different settings and sufficiently comparable studies meta-analysed. Results forty-nine heterogeneous studies were included. Community: meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85–1.29, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70–1.27, I 2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69–1.14, I 2 = 0%, 2 s) for injurious falls. Hospital: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74–1.28, I 2 = 15%, 2 s) and in an RR = 0.50 (0.07–3.50, I 2 = 72% %, 2 s) for number of fallers after and during admission, respectively. Long-term care: meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72–1.02, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64–1.35, I 2 = 92%, 7 s) for number of falls. Conclusions: the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls. PROSPERO registration number: CRD42020218231@en