After successful percutaneous coronary intervention (PCI), unpredictable coronary events occur that are caused by in-stent restenosis and the progression of preexisting nonculprit coronary lesions. However, little is known about the long-term clinically driven PCI rates for the progression of nonculprit coronary lesions discovered during culprit-lesion PCI or its independent predictors, including several biomarkers. In this study, the clinical and angiographic data of 1,395 PCI patients treated from January 2004 to May 2007 were retrospectively analyzed. Of these patients, 507 were eligible for this study. After baseline PCI (i.e., culprit-lesion PCI), 81 patients (16%) underwent additional clinically driven PCI to treat preexisting nonculprit coronary lesions during the study period. The cumulative rates of clinically driven PCI for nonculprit coronary lesions were 7.7% (n = 39) at 1 year, 14% (n = 70) at 2 years, and 16% (n = 81) at 3 years. The independent predictors of clinically driven PCI included a larger number of significant coronary lesions (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.5 to 3.5, p <0.001), low high-density lipoprotein (<40 mg/dl; OR 2.01, 95% CI 1.01 to 3.98, p = 0.046), hypercholesterolemia (total cholesterol >200 mg/dl; OR 1.46, 95% CI 1.22 to 1.97, p = 0.04), history of PCI (OR 1.24, 95% CI 1.09 to 1.60, p = 0.003), and increased triglyceride levels (OR 1.003, 95% CI 1.001 to 1.007, p = 0.038) at the time of baseline PCI. In conclusion, PCI patients with nonculprit coronary lesions underwent additional clinically driven PCI at rates of 7.7% at 1 year, 14% at 2 years, and 16% at 3 years because of the progression of preexisting nonculprit coronary lesions. Overall coronary artery disease burden and poor lipid profiles at baseline PCI confer significant risks for clinically driven PCI.