Introduction: There are limited data on the use of anticoagulation (AC) and anti-platelet (AP) agents in addition to aspirin compared to standard of care (aspirin alone) in cardiac arrest (CA) patients without ST-segment-elevation and not undergoing a percutaneous coronary intervention. Hypothesis: We hypothesized that use of AC/AP agents in CA is associated with lower mortality compared to aspirin alone. Methods: A comprehensive literature search was performed from inception to 09/30/2021 of the PubMed/EMBASE databases. Studies of adult patients comparing AC/AP to aspirin alone were evaluated for short-term mortality (30-days survival/survival to hospital discharge), significant bleeding, and return of spontaneous circulation (ROSC). Odds ratio (OR) with 95% confidence intervals (CI) were calculated using DerSimonian-Laird method. Results: Of a total 5337 studies, five studies (2 randomized trials and 3 observational studies) with 3,696 subjects (1,196 intervention and 2,500 placebo arm) were included. Overall, there was no evidence of publication bias using either funnel plot or eggers test. For RCT studies, mean age was 60.8 years (males 79.2%), while for observational study mean age was between 58 to 62.3 years (males 58-62.3%). Use of AP/AC was associated with higher rates of major bleeding (odds ratio [OR] = 2.43 [95% confidence interval {CI} 1.35- 4.37]; p=0.003; I2=7%; 4 studies) compared with aspirin alone. There was no significant difference in ROSC (OR= 1.24 [95% CI 0.68-2.26]; p=0.49; I2=57%; 3 studies) and short-term mortality [OR= 1.24 [95% CI 0.87-1.76]; p=0.24; I2=69%; 3 studies) between intervention and placebo arm. Conclusions: In this meta-analysis, use of concomitant AC/AP therapy with aspirin in CA without ST-segment-elevation or percutaneous coronary intervention was associated with higher rates of bleeding without improvement in short-term mortality or ROSC.