Patients with type 2 diabetes (T2DM) and hyperlipidemia are with high risk of myocardial infarction (MI) or coronary death events. The combined use of ezetimibe and atorvastatin could improve treatment efficacy and safety. To explore the efficacy and safety of ezetimibe in combination with atorvastatin for the treatment of patients with T2DM and acute coronary syndrome (ACS). This was a non-randomized cohort study of 95 consecutive, treatment-naïve patients with T2DM and ACS treated at the Quanzhou First Hospital of Fujian Province between February 2014 and March 2016. According to the treatment strategy they selected, the patients were categorized into the atorvastatin ( n = 46) and atorvastatin + ezetimibe ( n = 49) groups. The patients were followed up at 2 weeks and 12 months. The primary endpoints included the incidence of adverse cardiovascular events and changed in blood lipids and high-sensitivity C-reactive protein (hs-CRP). At 12 months, serum total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower, and high-density lipoprotein cholesterol (HDL-C) levels were significantly higher in the atorvastatin + ezetimibe (EZ) group than in the atorvastatin group (all p < 0.05). The LDL-C control rate at 12 months was significantly higher in the atorvastatin + EZ group compared with the atorvastatin group ( p = 0.006). Seven patients in the atorvastatin group were re-hospitalized for angina pectoris, while only one patient in the atorvastatin + EZ group was re-hospitalized for angina pectoris ( p = 0.02). The efficacy of atorvastatin + EZ in treating T2DM patients accompanied with ACS was significantly higher than using atorvastatin alone. This combined strategy has good safety profile, and could be recommended for clinical application.