The previously study found, using a mouse model, that acute myocardial infarction accelerated atherosclerosis. This study assessed whether ST elevation myocardial infarction (STEMI) accelerates the progression of non-culprit coronary lesion (NCCL) in patients who underwent percutaneous coronary interventions (PCI). Four hundred and forty-nine patients who underwent successful PCI with stents and follow-up coronary angiography in a single center were enrolled. The NCCL progression was assessed using three-dimensional quantitative coronary angiography and was defined as ≥10 % diameter reduction of a preexisting stenosis ≥50, ≥30 % diameter reduction of a stenosis <50 %, development of a new stenosis ≥30 % in a previously normal segment, or progression to total occlusion. The patients were classified into two groups according to whether the progression existed or not. The median age of patients was 58.4 years. The mean angiographic follow-up period was 12.3 months, 134 (29.8 %) patients had NCCL progression. Multivariate Cox regression analysis (step-wise) showed that STEMI was the only independent determinant of NCCL progression. Compared to the other coronary artery disease group, the crude hazard ratio (HR) of NCCL progression for the STEMI group was 3.20 (95 % CI 2.27-4.50; p < 0.001), and the association remained significantly after adjustment for age, sex, BMI, SBP, DBP, serum lipids, fasting blood glucose, peak monocyte count, smoking, drinking, hypertension, diabetes mellitus and lesion characteristics of NCCL (adjusted HR 3.56, 95 % CI 2.41-5.27; p < 0.001). The ST elevation acute myocardial infarction accelerates non-culprit coronary lesion atherosclerosis.