Aortic stenosis and coronary artery disease (CAD) frequently coincide. However, the management of coexisting CAD in patients undergoing transcatheter aortic valve replacement (TAVR) remains controversial. This study sought to determine whether the presence of CAD, its complexity, and angiography-guided percutaneous coronary intervention (PCI) are associated with outcomes after TAVR. All patients undergoing TAVR at a tertiary referral center between 2008 and 2020 were included in a prospective observational study. Baseline SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score (SS) and, whenever applicable, a residual SS after PCI were calculated. A multivariate analysis was performed to determine the effect of CAD, stratified according to complexity, and PCI on 5-year outcomes. In 604 patients, the presence of CAD and its complexity were significantly associated with worse 5-year survival (SS 0: 67.9% vs SS 1-22: 56.1% vs SS >22: 53.0%; log-rank P=0.027) and increased cardiovascular mortality (SS 0: 15.1% vs SS 1-22: 24.0% vs SS >22: 27.8%; log-rank P=0.024) after TAVR. Having noncomplex CAD (SS 1-22) was an independent predictor for increased all-cause mortality (HR: 1.43; P=0.046), while complex CAD (SS >22) increased cardiovascular mortality significantly (HR: 1.84; P=0.041). Angiography-guided PCI or completeness of revascularization was not associated with different outcomes. The presence of CAD and its anatomical complexity in patients undergoing TAVR are associated with significantly worse 5-year outcomes. However, angiography-guided PCI did not improve outcomes, highlighting the need for further research into physiology-guided PCI.