Transradial artery (TRA) approach is associated with fewer vascular complications and reduced mortality in patients at high risk compared with transfemoral approach (TFA). The objective of our study was to compare the characteristics and outcomes of patients who had coronary angiography by TRA and TFA over the course of hospital implementation of this approach. We included 12,928 patients from Baylor University Medical Center and Baylor Heart and Vascular Hospital, Dallas, Texas, who underwent a coronary angiography from January 2008 to March 2015. To control for selection bias and the learning curve, a nested matched study design was used for patients with percutaneous coronary intervention (PCI) with TRA patients matched with TFA by age (±2 years) and calendar year of the procedure in a ratio of 1:3. TRA for PCI increased from nearly 0% in 2008 to 9% in 2014. Including patients from 2011 to 2015 for the analysis, patients with TFA were older (65 ± 12 vs 64 ± 11) and had lower mean body mass index (30 ± 7 vs 33 ± 9 kg/m²) than patients with TRA. Patients with TRA had less bleeding, dialysis, pseudoaneurysm, and access site hematomas than the patients with TRA (0.7% vs 0%; p = 0.02). By a conditional logistic regression, we observed fewer complications, readmissions, and in-hospital deaths among TRA patients than the matched TFA patients. In conclusion, patients undergoing angiography with/without PCI through TRA had fewer complications, readmissions, and a shorter length of hospital stay after procedure versus TFA at our hospital.