Coronary angioplasty through smaller-diameter guiding catheters using predominantly fixed-wire balloon systems has been possible, but has had some limitations. The purpose of this prospective, nonrandomized study was to investigate the results of percutaneous transluminal coronary angioplasty using a new 6F guiding catheter with over-the-wire balloon systems. Coronary angioplasty using over-the-wire balloon systems through a new 6F guiding catheter was evaluated in 79 lesions in 70 patients and then compared to randomly selected procedures using 7F guiding catheters in 70 patients performed over the same time period. Coronary angioplasty through 6F guiding catheters and over-the-wire balloons including 8 long (30-mm) and 3 perfusion balloons was successful in 94.9% of lesions and in 94% of patients. Coronary angioplasty through 7F guiding catheters was successful in 97.5% of lesions and in 97.1% of patients, respectively. Success rates between 6F and 7F guiding catheter groups were similar overall and for proximal, mid, distal, or complex (total, subtotal, or length > 10-mm) lesions. There were no failures to withdraw the deflated balloon into the 6F guiding catheter. Vessel opacification after dilatation with the guidewire across the lesion was similar between the 6F and 7F guiding catheter groups. The mean change in hematocrit for the 6F procedures (-1.4 +/- 3.7%) was significantly lower than for the 7F procedures (-3.3 +/- 3.2%, P < 0.001). Coronary angioplasty using a variety of over-the-wire balloon catheters through a new 6F guiding catheter is feasible with success rates comparable to 7F guiding catheters. Angioplasty with this 6F guiding catheter reduces procedural blood loss compared to larger-lumen guiding catheters.