Objective To determine the effect of preoperative serum level of glycosylated hemoglobin (HbA1c) on the prognosis of elderly patients with acute coronary syndromes (ACS) after percutaneous coronary intervention (PCI) and investigate the rationality of peri-operative use of tirofiban. Methods A prospective study was performed in our hospital from January 2012 to March 2014 on the consecutive elderly ACS patients with coexisting diabetes mellitus and planing to undergo PCI. For the admitted 648 patients, they were divided into 3 groups according to preoperative serum level of HbA1c, that is, group A (HbA1c＜6.5%, n＝152), group B (6.5%≤HbA1c≤7.5%, n＝245) and group C (HbA1c＞7.5%, n＝251). The cohort was also assigned into group X (not use of tirofiban, n＝351) and group Y (using tirofiban, n＝297). The incidences of primary and secondary endpoints were compared among these groups. Multivariate COX regression analysis was used to analyze the risk factors for the major endpoints. Results (1) Significant difference was found in the incidence of major endpoints among group A, B and C (P＜0.01). The incidence was obviously higher in group X than in group Y [68(21.9%) vs 33(15.4%), P＜0.05]. In group X, the incidence had remarkable difference among group A, B and C (P＜0.01), but no such difference was observed in group Y. (2) Significant difference was only seen in the incidence of minimal bleeding events (secondary end points) between group X and Y (P＜0.01). (3) Tirofiban reduced the incidence of nonfatal myocardial infarction (MI) and in-stent restenosis for those with HbA1c＞7.5% (group C). (4) Multivariate COX regression analysis indicated that previous MI, previous PCI or coronary artery bypass surgery (CABG), history of smoking, HbA1c level and application of tirofiban were the independent risk factors for major endpoints in elderly ACS patients with coexisting diabetes mellitus within 1 year. Conclusion Preoperative HbA1c level is an important predictor for major endpoints in elderly diabetic patients with ACS after PCI. Combined peri-operative application of tirofiban reduces the incidence of the major endpoints, but increases the risk for bleeding events.