BackgroundMedication-related adverse events in primary care are a leading cause of hospital admissions and mortality, commonly resulting from medication errors. Previous reviews have assessed interventions broadly across healthcare settings, but few have focused specifically on interventions targeting medication errors in primary care.ObjectiveTo evaluate the effectiveness of professional, organisational, and structural interventions in primary care settings in reducing medication-related hospital admissions, emergency department (ED) visits, and mortality.MethodsWe conducted a systematic review using the Cochrane methodology of systematic reviews and PRISMA guidelines for reporting. A comprehensive search of CENTRAL, MEDLINE, Embase, CINAHL, and trial registries up to October 2024 was undertaken. Randomised controlled trials conducted in primary care that assessed the impact of interventions on hospital admissions, ED visits, and mortality were included. Cochrane Risk of bias assessments and random-effects meta-analyses were performed.ResultsInterventions were classified according to the Cochrane Effective Practice and Organisation of Care criteria into Professional, Organisational and Structural. Sixty-two studies met the inclusion criteria. Professional interventions, including educational training and clinical decision tools, showed little to no effect on primary outcomes (risk ratio [RR] 1.01, 95% confidence interval [CI] 0.94-7.00 for hospital admissions; RR 1.00, 95% CI 0.98-1.02 for mortality; very-low to low certainty evidence). Organisational interventions, such as pharmacist-led medication reviews and multidisciplinary care models reduced the number of hospital admissions (RR 0.81, 95% CI 0.70-0.95; low-certainty evidence), but had uncertain effects on ED visits and mortality. Structural interventions, such as system-level support and quality monitoring, showed a reduction in hospital admissions (RR 0.90, 95% CI 0.83-0.97; moderate-certainty evidence), but evidence for other outcomes showed limited or very-low certainty.ConclusionOrganisational and structural interventions in primary care may reduce medication-related hospital admissions and may help inform clinical practice through implementation of multidisciplinary care models and system-level quality monitoring approaches. However, the overall certainty of evidence is low to very low, highlighting the need for high-quality trials to better inform clinical practice and policy.