Limited data are available on long-term outcomes for vulnerable plaque analyzed by intravascular ultrasound (IVUS). The aim of this study was to investigate long-term clinical outcomes in 183 patients (79 with stable angina pectoris and 104 with acute coronary syndromes) who underwent preintervention 3-vessel IVUS and single-vessel stent implantation. Critical events, defined as any cause of death and acute coronary syndromes during follow-up, were evaluated. Plaque characteristics were analyzed in the target vessel and nontarget vessels. Vulnerable plaques were arbitrarily defined as plaques with rupture, lipid core, dissection, or thrombus. The mean follow-up period was 50 +/- 20 months. Critical events developed in 12 patients (7%; 6 acute coronary syndromes, 6 deaths). The critical event-free rate was not different according to the presence of vulnerable plaques in the target lesion (95% vs 95%, p = 0.86). However, in the nontarget vessels, the long-term critical event-free rate was significantly lower in patients with vulnerable plaques (88% vs 96%, p = 0.04). On multivariate Cox regression analysis, the multiplicity of vulnerable plaques in the nontarget vessels (hazard ratio 2.2, 95% confidence interval 1.4 to 3.4, p = 0.001) was the only independent predictor of long-term critical events. Acute coronary syndromes (odds ratio 5.4, 95% confidence interval 2.1 to 14.3, p = 0.001) and diabetes mellitus (odds ratio 5.2, 95% confidence interval 1.9 to 13.8, p = 0.001) were significantly associated with the multiplicity of vulnerable plaques. In conclusion, the multiplicity of vulnerable plaques in nontarget vessels was the most important predictor of future critical cardiac events in this 3-vessel IVUS study.