An increasing number of patients who have undergone previous coronary artery bypass grafting (CABG) are referred for percutaneous coronary revascularization. We identified patients who underwent percutaneous intervention for unstable angina from 1990 to 1998 at our institution and assigned them into 2 groups based on whether or not they had undergone previous CABG. There were 1,431 patients with and 4,629 patients without previous CABG. Previous CABG patients were older, had more atherosclerotic risk factors, more heart failure, lower ejection fraction, more multivessel disease, more multilesion treatment, more complex lesions, and less complete revascularization. Adjusting for baseline differences, previous CABG was associated with worse long-term mortality (RR 1.47, 95% confidence intervals [CI] 1.22 to 1.77, p < 0.001) and death, myocardial infarction, and/or revascularization (RR 1.16, 95% CI 1.04 to 1.30, p = 0.01); treatment of native lesions in patients with previous CABG versus treatment of vein graft lesions was associated with a reduction in this composite end point (RR 0.75, 95% CI 0.65 to 0.87, p < 0.001). Post-CABG patients treated between 1995 and 1998 had lower long-term mortality (RR 0.76, 95% CI 0.59 to 0.99, p = 0.04) and death, myocardial infarction, and/or revascularization (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001) compared with those treated between 1990 and 1994. Thus, in patients with unstable angina referred for percutaneous revascularization, previous CABG is associated with reduced event-free survival, although the outcome of post-CABG patients treated from 1995 to 1998 is superior to that observed in patients treated from 1990 to 1994. In patients who underwent previous CABG, treatment of native lesions affords better long-term outcome than vein graft intervention.