We compared 5 versus 6 French (Fr) guiding catheters in coronary intervention using the transradial approach. Smaller guiding catheters may have advantages over larger ones in transradial coronary intervention. However, there is uncertainty about how small is small enough, and when smaller would become too small. Eligible patients were randomized between the 5 and 6 Fr groups before the procedure. The primary endpoint was procedural success. A total of 216 patients were randomized. Procedural success was obtained in 95% of the 6 Fr group versus 90% of the 5 Fr group (p = 0.25). Most of the failures in the 5 Fr group were because of cross-over to the 6 Fr group. Crossover to the 5 Fr group occurred in 1 patient in the 6 Fr group (0.9%; p = 0.05) because of a small radial artery. Transradial intervention using 5 Fr guiding catheters necessitates crossover to a 6 Fr catheter in 6.8% of cases, and offers no clear advantages over the 6 Fr technique.