Background: Trans-radial approach (TRA) reduces vascular access-site complications but has some technical limitations. Usually, TRA procedures are performed using 5 Fr or 6 Fr sheaths, whereas complex interventions requiring larger sheaths are approached by trans-femoral access. Methods: During 4 years, at two Institutions with high TRA use, we have attempted to perform selected complex coronary or peripheral interventions by TRA using sheaths larger than 6 Fr. Clinical and procedural data were prospectively collected. Attempt to place a 7 Fr or 8 Fr sheath (according to the planned strategy of the procedure) was performed after 5–6 Fr sheath insertion, administration of intra-arterial nitrates and radial artery angiography. Late (>3 months) patency of the radial artery was checked (by angiography in the case of repeated procedures or by palpation + reverse Allen test). Results: We collected 60 patients in which TRA large sheath insertion was attempted. The large sheath (87% 7 Fr, 13% 8 Fr) was successfully placed in all cases. Most of the procedures were complex coronary interventions (bifurcated or highly thrombotic or calcific chronic total occlusive lesions), whereas 8.3% were carotid interventions. Procedural success rate was 98.3% (1 failure to reopen a chronic total occlusion). No access-site related complication occurred. In 57 (95%) patients, late radial artery patency was assessed and showed patency in 90% of the cases, the remaining patients having asymptomatic collateralized occlusion. Conclusions: In selected patients, complex percutaneous interventions requiring 7–8 Fr sheaths can be successfully performed by RA approach without access-site clinical consequences. © 2011 Wiley Periodicals, Inc.