AimsPrevious systematic reviews suggest that deprescribing may improve survival, particularly in frail older people. Evidence is rapidly accumulating, suggesting a need for an updated review of the literature.MethodsWe updated a 2016 systematic review and meta‐analysis to include studies published from inception to 26 April 2024 from specified databases. Studies in which older people had at least one medication deprescribed were included and grouped by study designs and targeted medications. The risk of bias was assessed using the Cochrane tool and the Newcastle‐Ottawa tool. Odds ratios (OR) or mean differences were calculated as the effect measures using either the Mantel–Haenszel or generic inverse‐variance method with fixed‐ or random‐effects meta‐analyses. The primary outcome was mortality. Secondary outcomes were adverse drug withdrawal events, physical health, cognitive function, quality of life and effect on medication regimen. Subgroup analyses were performed based on age and intervention types.ResultsA total of 259 studies (reported in 286 papers) were included in this updated review. Deprescribing polypharmacy did not result in a significant reduction in mortality in both randomized (OR 0.96, 95% confidence interval [CI] 0.84–1.09) and non‐randomized studies (OR 0.70, 95% CI 0.36–1.38). Further subgroup analyses of randomized studies on deprescribing polypharmacy demonstrated a significant reduction in mortality in the young old (aged 65–79) (OR 0.71, 95% CI 0.51–0.99) and when patient‐specific interventions were applied (OR 0.79, 95% CI 0.63–0.99).ConclusionsDeprescribing can be achieved with potentially important benefits in terms of improved survival, particularly when patient‐specific interventions are applied and initiated early in the young old.