Transradial coronary interventions (TCI) are occasionally limited by radial spasms and postprocedural radial occlusions, which are related to the radial diameter and which possibly may be reduced by the use of smaller guiding catheter. However, 5 Fr, 0.058" lumen diameter guiding catheter affords less strength, visibility, and backup. In a randomized study, we investigated procedural and clinical success and vascular access complications of 5 Fr in comparison to 6 Fr guiding catheter. One hundred seventy-one patients with coronary lesions suitable for at least 5 Fr transradial approach (i.e., normal Allen test, only balloon angioplasty and stent) were randomly assigned for 5 or 6 Fr TCI. The primary combined endpoint was procedural and clinical success, and secondary endpoints were vascular access complications and the occurrence of postprocedural radial occlusions at 1-month follow-up. Procedural success was achieved in 95.4% of 5 Fr and 92.9% of 6 Fr patients. Selective cannulation of the coronary ostium failed in 1.1% of 5 Fr and 4.8% of 6 Fr patients (P = 0.08). Minor hematomas without need for surgical repair or blood transfusions occurred in 1.1% (5 Fr) and 4.8% (6 Fr; P = 0.07); 1.1% of 5 Fr and 5.9% of 6 Fr patients (P = 0.05) suffered loss of radial pulse due to radial occlusion. Selected noncomplex coronary lesions can successfully and safely be treated either with 5 or 6 Fr guiding catheters. A tendency of higher procedural success rates and lower vascular access complications was documented after 5 Fr in comparison to 6 Fr TCI. This was particularly the case among patients with small radial diameters.