Percutaneous coronary intervention (PCI) has emerged as a cornerstone therapy for coronary artery disease (CAD), the leading cause of morbidity and mortality worldwide. This study explores the comparative outcomes of radial and femoral access in PCI, particularly within high-risk patient subgroups, utilizing advanced antithrombotic therapies and radial-specific devices. Radial access demonstrated significant reductions in bleeding and vascular complications, especially among elderly patients, women, and those with acute coronary syndromes (ACS). Predictive models, incorporating patient-specific risk factors, highlighted the synergistic novel anticoagulants and specialized devices. Despite a modest increase key words: benefits of radial access combined with in fluoroscopy time, radial access was associated with shorter hospital stays and enhanced procedural safety. These findings underscore the importance of adopting radial access as a preferred PCI approach, paving the way for personalized interventions and advancing clinical guidelines to optimize outcomes across diverse populations.