Smaller guiding catheters can help reduce local complications and patient morbidity during transradial coronary intervention (TRI). This study was designed to compare the patient's morbidity, success rate, and the operator's convenience between 5-French (5Fr) and 6-French (6Fr) TRIs. This is a single-center prospective randomized study. Patients who underwent TRI, in 2003, were prospectively randomized to either 5Fr or 6Fr catheter groups (100 patients in each group). Procedure-related patient morbidity as well as clinical and procedural characteristics was scored and analyzed. Procedural success rate was not significantly different between the groups. The number of unsatisfactory supports (6% in 5Fr group, 3% in 6Fr group; P=0.31) and the incidence of local wound complications were not significantly different between the groups. Local wound pain scores were significantly lower in the 5Fr group compared with the 6Fr group, particularly during sheath insertion and removal, and during procedures. Pain scores were higher in female patients than in male patients during sheath removal (male: 1.3+/-1.3, female: 1.7+/-1.5; P=0.049). Radial artery diameter was well correlated with local pain score during sheath removal (r=0.31, P<0.001), and with the height and weight of the patients (height: r=0.33, P<0.001; weight: r=0.27, P<0.001). In conclusion, using a 5Fr catheter during TRI reduce, local access site pain, particularly in female patients with smaller body size, whereas the success and local complication rates were similar to a 6Fr approach.