Abstract Background The prevalence of coronary artery disease (CAD) in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation (TAVI) is high. However, the importance of a percutaneous coronary intervention (PCI) prior to TAVI has been matter of debate. Importantly, patients undergoing TAVI are characterized by high age often accompanied by highly calcified coronary arteries, increasing the risk of severe periprocedural complications. Moreover, patients with a severe aortic valve stenosis are limited in their ability to compensate for these life-threatening complications. Together with the necessity of dual antiplatelet therapy after PCI, this may explain a possible negative effect of PCI in this patient population. However, there is still insufficient evidence regarding the importance of PCI in patients undergoing TAVI. Purpose The aim of this systematic review and meta-analysis was to assess the need for PCI in patients with significant CAD undergoing TAVI. Methods A systematic search was conducted to identify studies comparing optimal medical treatment only versus PCI in patients with significant CAD undergoing TAVI. Endpoints were all-cause mortality, cardiac death, stroke, myocardial infarction, and major bleeding which were assessed at 30 days, one year, and beyond one year following TAVI. Results A total of 14 studies was included in this meta-analysis, including 3838 patients of which 1806 patients (47.1%) underwent PCI before TAVI. All-cause mortality was not significantly different between optimal medical treatment only and PCI at 30 days (OR: 1.27; 95% CI, 0.91–1.77; p=0.17; I2=0%), at one year (OR: 0.91; 95% CI, 0.64–1.29; p=0.59; I2=45%), and beyond one year (OR 0.68; 95% CI, 0.42–1.08; p=0.10; I2=49%). Cardiac death and myocardial infarction was similar across the groups at 30 days (OR cardiac death: 1.94; 95% CI, 0.36–10.56; p=0.45; I2=28%; OR myocardial infarction: 0.50; 95% CI, 0.13–1.91; p=0.31; I2=0%), and at one year (OR cardiac death: 0.77; 95% CI, 0.19–3.13; p=0.72; I2=84%; OR myocardial infarction: 0.74; 95% CI, 0.21–2.66; p=0.64; I2=18%). Stroke did not significantly differ between PCI and optimal medical treatment groups at 30 days (OR: 0.77; 95% CI, 0.31–1.92; p=0.57; I2=0%). However, patients that underwent TAVI without preceding PCI had significantly lower risk of major bleeding at 30 days (OR: 0.66; 95% CI, 0.46–0.94; p=0.022; I2=0%). Conclusion This systematic review and meta-analysis showed no significant differences in clinical outcomes between patients with and without PCI prior to TAVI at both short- and long-term follow-up, apart from a higher risk of major bleeding within 30 days in patients undergoing PCI before TAVI. Funding Acknowledgement Type of funding sources: None.