Funding Acknowledgements Type of funding sources: None. Background Stroke during Transcatheter Aortic Valve implantation (TAVI) is not an uncommon complication with potential devastating consequences. With the extension of TAVI to the low-risk patient, stroke prevention takes on increasing importance. The use of cerebral embolic protection device (EPD) reveals conflicting data. This meta-analysis aims to evaluate the clinical efficacy and safety of EPDs. Methods A comprehensive literature search for all studies till May 2022 reporting clinical safety and efficacy outcomes of the only EPD approved for use by the Food and Drug Administration (FDA) was performed. Study outcomes were divided based on time period - overall (up to 30 days and in-hospital) and short (≤7 days). Primary outcome was stroke - major and minor. Secondary outcomes included transient ischaemic attack (TIA), mortality, acute kidney injury (AKI), major vascular and bleeding complications. Results A total of 12 studies involving 288531 patients were analysed, which included 3 randomised controlled trials (RCTs), 7 propensity-matched and 2 cohort studies. Regarding overall outcomes, significant differences were noted for mortality (OR 0.59 [0.42-0.84], p=0.0036) and major stroke (OR 0.40 [0.18-0.91], p=0.028) (Fig 1). No significant differences were noted for all stroke (p=0.058), minor stroke (p=0.32), TIA (p=0.49), AKI (p=0.17), major vascular complications (p=0.40) and major bleeding complications (p=0.11). There was significant heterogeneity across the studies for mortality (p=0.032) and all stroke (p=0.009). In the subgroup analysis of studies reporting ≤7 days outcomes (n=5), EPDs showed significantly lower rates of all stroke (0.33 [95% CI 0.19-0.56], p=<0.0001), major stroke (0.19 [0.08-0.48], p=0.0004) and major bleeding complications (OR 0.29 [0.10-0.79], p=0.016), but no significant differences for mortality (p=0.67) and minor stroke (p=0.070). There was no significant heterogeneity across the studies (all p>0.05) Conclusions In this meta-analysis including non-randomised studies, the use of EPDs was associated with lower mortality and major stroke rates, although significant heterogeneity was noted for the studies reporting mortality. Further ongoing larger scale RCTs will further clarify these results.