Objective To compare 5 French (Fr) and 6 Fr guiding catheters regarding the volume of contrast administered, fluoroscopy time, and total procedure time during transradial percutaneous coronary intervention (PCI). Background Previous studies had compared 5 Fr and 6 Fr catheters and deemed 5 Fr catheters safe and effective. In this study, we retrospectively compared the 5 Fr catheter to 6 Fr catheter with an attempt to eliminate the effect of inter-operator skill level variability. Methods In a single-center, retrospective cohort study, we randomly selected patients who had received PCI through transradial access using 5 Fr or 6 Fr catheters. The study involved two groups of 100 patients each. These groups were comprised of an equal number of cases from each operator. The primary endpoint was contrast medium volume. Secondary endpoints were fluoroscopy time and procedure time. Results Less contrast was used in the 5 Fr group vs. 6 Fr catheter group (140.2 ± 45.7 mL vs. 158.2 ± 66.7 mL, p=0.004). PCI using 5 Fr catheters was associated with shorter fluoroscopy time (13.7 ± 7.3 mins vs. 15.2 ± 8.2 mins, p=0.584) and shorter procedure time (43.7 ± 22.2 mins vs. 46.5 ± 19.7 mins, p=0.890), but this was not statistically significant. Conclusion Transradial PCI using 5 Fr guiding catheters was associated with less contrast medium usage, but there was no advantage regarding procedure time or fluoroscopy time when compared to 6 Fr catheters. Similar to 6 Fr catheters, 5 Fr catheters achieved high PCI success rates through radial access when compared in the treatment of coronary lesions with the same level of complexity.