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Background: Patients 65 years old and older largely represent (>50%) hospital-admitted patients with acute coronary syndrome (ACS). Data are conflicting comparing efficacy of early routine invasive (within 48-72 hours of initial evaluation) versus conservative management of ACS in this population., Objective: We aimed to determine the effectiveness of routine early invasive strategy compared to conservative treatment in reducing major adverse cardiovascular events in patients 65 years old and older with non-ST elevation (NSTE) ACS., Data Sources: We conducted a systematic review of randomized controlled trials (RCTs) through PubMed, Cochrane, and Google Scholar database., Study Selection: The studies included were RCTs that evaluated the effectiveness of invasive strategy compared to conservative treatment among patients ≥ 65 years old diagnosed with NSTEACS. Studies were included if they assessed any of the following outcomes of death, cardiovascular mortality, myocardial infarction (MI), stroke, recurrent angina, and need for revascularization. Six articles were subsequently included in the meta-analysis., Data Extraction: Three independent reviewers extracted the data of interest from the articles using a standardized data collection form that included study quality indicators. Disparity in assessment was adjudicated by another reviewer., Data Synthesis: All pooled analyses were initially done using Fixed Effects model. For pooled analyses with significant heterogeneity (I2≥ 50%), the Random Effects model was used. A total of 3,768 patients were included, 1,986 in the invasive strategy group, and 1,782 in the conservative treatment group., Results: Meta-analysis showed less incidence of revascularization in the invasive (2%) over conservative treatment groups (8%), with overall risk ratio of 0.29 (95% CI 0.14 to 0.59). Across all pooled studies, no significant effect of invasive strategy on all-cause mortality, cardiovascular mortality, stroke, and MI was observed. Only one study assessed the outcome of recurrent angina., Conclusion: There was a significantly lower rate of revascularization in the invasive strategy group compared to the conservative treatment group. In the reduction of all-cause mortality, cardiovascular mortality, MI, and stroke there was no significant effect of invasive strategy versus conservative treatment. This finding does not support the bias against early routine invasive intervention in patients ≥ 65 years old with NSTEACS. Further studies focusing on these patients with larger population sizes are still needed., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RRC is a member of advisory board or speakers’ pool of Servier, Boehringer Ingelheim, Menarini, LRI-Therapharma, Sanofi, UAP Pharma, Unilab; MTR is a member of speakers’ pool of Novartis, Servier, Astra Zeneca; the rest declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.