Objectives To study the causes of and to develop a risk score for failure of transradial approach (TRA) for percutaneous coronary intervention (PCI). Background TRA-PCI failure has been reported in 5% to 10% of cases. Methods TRA-PCI failure was categorized as primary (clinical reasons) or crossover failure. Multivariate analysis was performed to determine independent predictors of TRA-PCI failure, and an integer risk score was developed. Results From January to June 2010, TRA-PCI was attempted in 1,609 (97.3%) consecutive patients, whereas 45 (2.7%) had primary TRA-PCI failure. Crossover TRA-PCI failure occurred in 30 (1.8%) patients. Causes of primary TRA-PCI failure included chronic radial artery occlusion (11%), previous coronary artery bypass graft (27%), and cardiogenic shock (20%). Causes for crossover TRA-PCI failure included: inadequate puncture in 17 patients (57%); radial artery spasm in 5 (17%); radial loop in 4 (13%); subclavian tortuosity in 2 (7%); and inadequate guide catheter support in 2 (7%) patients. Female sex (odds ratio OR: 3.2; 95% confidence interval CI: 1.95 to 5.26, p < 0.0001), previous coronary artery bypass graft (OR: 6.1; 95% CI: 3.63 to 10.05, p < 0.0001), and cardiogenic shock (OR: 11.2; 95% CI: 2.78 to 41.2, p = 0.0011) were independent predictors of TRA-PCI failure. Risk score values from 0 to 7 predicted a TRA-PCI failure rate from 2% to 80%. Conclusions In a high-volume radial center, 2.7% of patients undergoing PCI are excluded from initial TRA on clinical grounds, whereas crossover to femoral approach is required in only 1.8% of the cases. A new simple clinical risk score is developed to predict TRA-PCI failure.