Objectives:To investigate the relationship between the changes of blood lipids and the progression of non-target lesions after percutaneous coronary intervention (PCI). Methods:Consecutive patients hospitalized in Beijing Anzhen Hospital of Capital Medical University from January 2013 to December 2016 for acute coronary syndrome (ACS) with coronary angiography evidence of multivessel disease, in which single vessel disease (Target lesion) stenosis＞ 75%, and the single vessel was treated with PCI, and the remaining non-target lesions with stenosis ＜50%, and re-hospitalized due to chest pain within 6 to 24 months, were eligible for this study. A total of 3 071 patients met the inclusion criteria were enrolled in this study. According to the quantitative analysis of 3-dimensional reconstruction coronary angiography (QCA), patients were divided into A, B groups:group A (n=1 541) refers patients with progressive non-target lesions (stenosis from ＜50% to ＞75%), group B (n=1 530) refers progression-free non-target lesions (stenosis ＜75%). Blood lipid levels at two hospitalizations, blood lipid changes and the lipid control rate, LDL-C control rate = (＜1.8 mmol/L patients + LDL-C decline＞50%)/ total number of patients, were compared between the two groups. Results:The LDL-C level [group A:(2.68 ± 0.88) mmol/L vs group B:(2.72 ± 0.92) mmol/L, P=0.509] and the LDL-C control rate (group A:14% vs group B:13.1%, P=0.476) at the first hospitalization were similar between the two groups. At the second hospitalization, the level of LDL-C was significantly lower in group B than that in group A ([1.91 ± 0.64] mmol/L vs [2.17 ± 0.76] mmol/L, P＜0.001). The LDL-C control rate was significantly higher in group B than in the group A (43.66% vs 35.37%, P＜0.001). Moreover, the reduction of total cholesterol and triglyceride was more significant in group B ([0.85±0.81] mmol/L and [0.24±1.58] mmol/L) compared to group A ([0.58±1.01] mmol/L and [0.17±1.37] mmol/L, both P＜0.001) at the second hospitalization. Multivariate Logistic regression analysis showed that age, diabetes, hypertension, smoking, family history of coronary heart disease, hyperlipidemia and non-target lesions were not associated with progression of non-target lesions; LDL-C level at the second hospitalization (OR=1.686, 95%CI:1.508~1.885; P＜0.001) and regular statin use after PCI (OR=0.275, 95%CI:0.230~0.328; P＜0.001) were associated with progression of non-target lesions. Conclusions:Our results indicate that poor lipid control post PCI is one of the reasons leading to the progression of non-target lesions.