This study evaluated the feasibility of performing coronary angioplasty through 6F diagnostic catheters by mainly using over-the-wire balloon systems on 84 lesions in 70 patients. Procedural variables, including vessel opacification and angioplasty outcome, were assessed. Changes in hematocrit after angioplasty were compared for 6F versus 7F and 8F systems. Successful 6F dilatation was performed in 72 (85.7%) of 84 lesions and 58 (82.9%) of 70 patients. Seven of the 12 lesions unable to be dilated with 6F systems were successfully dilated with larger French systems. Coronary artery opacification with the 6F catheters after balloon dilation was less than optimal with the balloon and guidewire still in the catheter. Changes in hematocrit after 6F procedures were significantly less than for 8F procedures (-2.1% vs -4.2%, respectively, p < 0.01) but not for 7F procedures (-2.4%, p = not significant). Potential cost savings for angioplasty with 6F diagnostic catheters could be significant. Thus angioplasty with over-the-wire balloon systems in which 6F nontapered diagnostic catheters are used can be performed safely and with less procedural blood loss than with 8F systems. Significant problems encountered with the current catheter design were poor vessel opacification after balloon dilation and difficulties with balloon retraction.