It has been proposed that directional coronary atherectomy (DCA) should be an intervention of choice in larger vessels as one can achieve a greater minimal luminal diameter with DCA than with percutaneous transluminal coronary angioplasty (PTCA). This in turn should translate into a higher success rate and may even reduce the restenosis rate. The aim of this study was to compare DCA versus PTCA in vessels >3mm in diameter. One hundred fifty consecutive patients who met the inclusion criteria and had DCA were compared to 150 similarly selected PTCA patients. PTCA patients were selected from the era immediately preceding the advent of DCA so that selection bias could be excluded. All patients with ostial lesions, restenosis, vessels <3mm in diameter, and vessels with more than two significant lesions were excluded. Distal segments and circumflex cases were excluded as they formed a small subsegment. Both groups were similar in terms of demographic, clinical and angiographic variables. Quantitative analysis showed that the initial net gain was significantly greater in the DCA group than in the PTCA group (2.36±0.8mm vs. 1.78±0.7mm; p<0.05). Residual stenosis was 11% with DCA compared to 33% with PTCA (p<0.05). Despite these improved anatomical results the procedural success rates were similar (91.5% vs 84%). Major in hospital complications (death, acute occlusion, MI, emergency CABG, re-do) were higher in the DCA group than in the PTCA group (12% vs 6%). Clinical follow-up on 276 patients (150 DCA vs 126 PTCA) showed a 6 month clinical restenosis rate of 18% vs 28%, respectively. The incidence of re-do in 24 hours for acute occlusion was 6% for DCA and 1% for PTCA. In large-sized vessels DCA results in a lower restenosis rate. However, despite a lower incidence of residual stenosis, the complication rate tends to be higher with DCA (p<0.05).