Objectives: The aim of this prospective, multicenter study was to assess the safety, feasibility, acceptance, and cost of ambulatory transradial percutaneous coronary intervention (PCI) under the conditions of everyday practice. Background: Major advances in PCI techniques have considerably reduced the incidence of post‐procedure complications. However, overnight admission still constitutes the standard of care in most interventional cardiology centers. Methods: Eligibility for ambulatory management was assessed in 370 patients with stable angina referred to three high‐volume angioplasty centers. On the basis of pre‐specified clinical and PCI‐linked criteria, 220 patients were selected for ambulatory PCI. Results: The study population included a substantial proportion of patients with complex procedures: 115 (52.3%) patients with multivessel coronary artery disease, 50 (22.7%) patients with multilesion procedures, and 60 (21.5%) bifurcation lesions. After 4‐6 hr observation period, 213 of the 220 patients (96.8%) were cleared for discharge. The remaining seven (3.2%) patients were kept overnight for unstable angina (n = 1), atypical chest discomfort (n = 2), puncture site hematoma (n = 1), or non‐cardiovascular reasons (n = 3). Within 24 hr after discharge, no patients experienced readmission, stent occlusion, recurrent ischemia, or local complications. Furthermore, 99% of patients were satisfied with ambulatory management and 85% reported no anxiety. The average non‐procedural cost was lower for ambulatory PCI than conventional PCI (1,230 ± 98 Euros vs. 2,304 ± 1814 Euros, P < 10−6). Conclusions: Ambulatory PCI in patients with stable coronary artery disease is safe, effective, and well accepted by the patients. It may both significantly reduce costs and optimize hospital resource utilization. © 2012 Wiley Periodicals, Inc.