Aim To explore the influencing factors of major adverse cardiovascular events (MACE) after drug-eluting stent (DES) implantation in young and middle-aged patients with coronary artery disease (CAD). Methods Retrospective study data from the First Affiliated Hospital of Zhengzhou University were extracted from the Dryad database, and young and middle-aged CAD patients who received DES were divided into MACE group (n＝57) and non MACE group (n＝321) according to whether MACE occurred during the follow-up period. Clinical data including age, gender etc. were compared between the two groups, and the variables with significant differences between the two groups were substituted into Logistic regression model to screen the influencing factors of MACE after DES implantation in young and middle-aged CAD patients. Value of influencing factors predicting occurrence of MACE after DES implantation in young and middle-aged CAD patients was evaluated by plotting ROC curve and calculating the area under the curve (AUC). ResultsStent diameter in MACE group was significantly smaller than that in non MACE group (P＜0.001), the number of left main coronary artery lesion in MACE group was significantly higher than that in non MACE group (P＜0.05). Multivariate Logistic regression analysis indicated that stent diameter (OR＝0.4,5%CI:0.084～0.405, P＜0.001) and left main coronary artery lesion (OR＝9.9,5%CI:2.291～37.904, P＝0.002) were the independent risk factors of MACE after DES implantation in young and middle-aged CAD patients. The risk of MACE after DES implantation in young and middle-aged CAD patients significantly decreased when the stent diameter was ＞3 mm. The AUC of stent diameter combined with left main coronary artery lesion predicting occurrence of MACE after DES implantation in young and middle-aged CAD patients was 0.700 (95%CI:0.623～0.776). Conclusion The smaller stent diameter and left main coronary artery lesion are the influencing factors of the occurrence of MACE after DES implantation in young and middle-aged patients with CAD, and should be emphasized by clinical practitioners.