Coronary angiography using 4 Fr catheters may reduce access site complications, promote better utilization of outpatient facilities, but at a cost of suboptimal image quality. To determine whether 4 Fr diagnostic angiography with power injection (Acist, Minneapolis, MN) was equivalent to 6 Fr manual technique, 101 unselected patients were randomized to transfemoral coronary angiography with 4 or 6 Fr catheters. Procedural characteristics, angiographic quality scores, and results of 90 min ambulation were analyzed. Coronary angiographic quality scores using 4 Fr and 6 Fr catheters were equivalent (left coronary artery 4.73 +/- 0.6 vs. 4.80 +/- 0.65, P = 0.28; right coronary artery 4.98 +/- 90.13 vs. 4.97 +/- 0.16, P = 0.48). However, 4 Fr left ventriculographic image score was lower (4.53 +/- 0.68 vs. 4.83 +/- 0.42, P = 0.0002), attributed, in part, to a smaller injected contrast volume (32 +/- 11 vs. 37 +/- 4 mL, P = 0.001). The total study contrast volume was significantly less in the 4 Fr group (119 +/- 35 vs. 159 +/- 52 mL, P = 0.001). Complications related to early ambulation at 90 min were similar and minimal in both groups. Compared to 6 Fr manual contrast injection technique, diagnostic angiography through 4 Fr catheters with power contrast injection resulted in equivalent coronary angiographic image quality, slightly reduced but diagnostic left ventricular image quality, and significantly less contrast volume. Four Fr angiography facilitates early ambulation without compromising safety and image quality.