Objective: This study aimed to assess the association between plasma bone morphogenetic protein-2 (BMP-2) level and in-stent restenosis in patients with coronary artery disease. Methods: A total of 96 patients who underwent percutaneous coronary intervention (PCI) and were followed up after PCI were enrolled in this study. 47 patients diagnosed with in-stent restenosis (ISR) were recruited to ISR group and 49 patients without ISR were recruited to Control group according to the results of coronary angiography (CAG). Baseline characteristic data were collected, and plasma BMP-2 level was evaluated. The results were analyzed using logistic regression. Results: There were 47 patients in the ISR group and 49 patients in the Control group. Plasma levels of BMP-2 were higher in the ISR group than in the non-ISR group [20.96 (18.44, 27.05) pg/ml vs. 29.53 (25.03, 34.07) pg/ml, P < 0.01]. Furthermore, the ISR group had significantly longer stent lengths and lower stent diameters than the Control group (P < 0.01 and P < 0.01, respectively). In multivariate analysis, BMP-2 level, diabetes, stent length and stent diameter were independently associated with ISR [odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.03-1.18, P < 0.01; OR = 4.75, 95% CI = (1.44-15.61), P = 0.01; OR = 1.06, 95% CI = (1.02-1.11), P < 0.01; and OR = 0.15, 95% CI = (0.02-0.95), P = 0.04, respectively]. Conclusions: Increased BMP-2 levels were independently associated with ISR in patients with coronary artery disease. Plasma BMP-2 may be useful in predicting ISR.