Objective Despite achieving very low levels of low-density lipoprotein cholesterol (LDL-C), many patients continue to show disease progression. We sought to characterize the clinical factors that correlate with nonculprit lesion plaque progression in patients with LDL-C level less than 1.8 mmol/l. Methods Between May 2006 and December 2009, 653 patients met the following criteria: (i) underwent coronary angiograms again with a time interval from 6 months to 2 years after successful stent implantation, (ii) less than 50% stenoses of nonintervened nonculprit coronary lesions (NCLs), (iii) follow-up LDL-C levels less than 1.8 mmol/l. Patients were classified as progressors [NCL-percutaneous coronary intervention (PCI)] or nonprogressors (non-NCL-PCI). Results Five patients with de novo NCL and 87 patients with preexisting NCL developed progression. Progressors had higher percentage of acute coronary syndrome (ACS), multivessel diseases and triglycerides (TGs) at baseline PCI. At follow-up, a significant difference was observed between progressors and nonprogressors in TG (1.73 vs. 1.32 mmol/l, P < 0.001), change in TG (-0.18 +/- 1.01 vs. -0.42 +/- 1.02 mmol/l, P = 0.032), high-density lipoprotein cholesterol (HDL-C) (0.98 +/- 0.22 vs. 1.08 +/- 0.25 mmol/l, P = 0.001) and change in HDL-C (0.11 +/- 0.17 vs. 0.19 +/- 0.27 mmol/l, P < 0.001). Multivariate logistic regression analysis revealed that ACS, multivessel diseases, on-treatment TG and HDL-C and smaller increases in HDL-C were independent predictors for progression. Conclusion Despite attainment of LDL-C level less than 1.8 mmol/l, NCL had still progressed, mainly in preexisting NCL rather than de novo NCL. ACS, multivessel diseases, on-treatment TG, HDL-C and smaller increases in HDL-C were associated with the NCL progression. This finding highlights the need for intensive modification of global risk in patients with coronary artery disease. Coron Artery Dis 22:49-54 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.