Periprocedural bleeding and vascular complications after percutaneous coronary intervention (PCI) are associated with worse clinical outcomes and increased short- and long-term mortality. Vascular access-related bleeding accounts for more than 80% of all major bleeding events in PCI performed by the transfemoral approach. Transradial approach (TRA), on the other hand, virtually eliminates access site bleeding and vascular complications. Although clinical trials have mostly evaluated different pharmacological strategies for reducing bleeding risk, adoption of a radial rather than a femoral access may allow greater reductions in bleeding complications than pharmacological strategies alone. High-risk patients such as those with acute coronary syndrome and ST-segment elevation myocardial infarction, women, obese patients, and elderly subjects who are at increased risk for vascular complications and bleeding might particularly benefit from the radial approach. Besides increased patient safety, the TRA is associated with improved patient satisfaction, reduced cost, and length of hospital stay, thus allowing outpatient performance of uncomplicated PCI.