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Objective: To assess the efficacy of medication review as an isolated intervention and with several co-interventions for preventing hospital readmissions in older adults., Methods: Ovid MEDLINE, Embase, The Cochrane Central Register of Controlled Trials and CINAHL were searched for randomized controlled trials evaluating the effectiveness of medication review interventions with or without co-interventions to prevent hospital readmissions in hospitalized or recently discharged adults aged ≥65, until September 13, 2019. Included outcomes were "at least one all-cause hospital readmission within 30 days and at any time after discharge from the index admission.", Results: Twenty-five studies met the inclusion criteria. Of these, 11 studies (7,318 participants) contributed to the network meta-analysis (NMA) on all-cause hospital readmission within 30 days. Medication review in combination with (a) medication reconciliation and patient education (risk ratio (RR) 0.45; 95% confidence interval (CI) 0.26-0.80) and (b) medication reconciliation, patient education, professional education and transitional care (RR 0.64; 95% CI 0.49-0.84) were associated with a lower risk of all-cause hospital readmission compared to usual care. Medication review in isolation did not significantly influence hospital readmissions (RR 1.06; 95% CI 0.45-2.51). The NMA on all-cause hospital readmission at any time included 24 studies (11,677 participants). Medication review combined with medication reconciliation, patient education, professional education and transitional care resulted in a reduction of hospital readmissions (RR 0.82; 95% CI 0.74-0.91) compared to usual care. The quality of the studies included in this systematic review raised some concerns, mainly regarding allocation concealment, blinding and contamination., Conclusion: Medication review in combination with medication reconciliation, patient education, professional education and transitional care, was associated with a lower risk of hospital readmissions compared to usual care. An effect of medication review without co-interventions was not demonstrated. Trials of higher quality are needed in this field., (© 2021 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)