Background Major vascular complications have been associated with increased mortality and morbidity in patients undergoing transcatheter aortic valve replacement (TAVR). Our objective was to compare vascular and bleeding outcomes with the routine use of 2-dimensional ultrasonography (2D-US) guided femoral artery access in percutaneous transfemoral TAVR compared with traditional anatomic landmark palpation with angiographically-guided access. Methods This single-centre retrospective cohort study was conducted in Ontario, Canada. We enrolled patients from January 1, 2012-June 30, 2016. Routine 2D-US was used in all transfemoral TAVR after January 1, 2014; before this, all cases were performed with angiographic guidance alone. Results The primary outcome of interest was the composite of any access-related red blood cell transfusion or vascular/bleeding complications. Definitions were based on the Valve Academic Research Consortium (VARC-2) criteria. Fully adjusted multivariable regression models were developed to determine the impact of 2D-US. The study cohort included 387 patients, 109 (28%) of whom underwent femoral artery puncture guided by anatomic and angiographic landmarks, whereas 278 (72%) patients had 2D-US guidance. After adjusting for baseline differences in our multivariable models, we found that 2D-US–guided access was associated with an odds ratio of 0.42 (95% confidence interval, 0.25-0.70; P < 0.01) for the composite end point of access-related vascular or bleeding complications and red blood cell transfusion. Conclusions The routine use of 2D-US in transfemoral TAVR was associated with substantial reductions in access-related vascular and bleeding complications.