OBJECTIVE Acute glucose fluctuations are associated with hypoglycemia and are emerging risk factors for cardiovascular outcomes. However, the relationship between glycemic variability (GV) and the occurrence of midterm major cardiovascular events (MACE) in patients with diabetes remains unclear. This study investigated the prognostic value of GV in patients with diabetes and acute coronary syndrome (ACS). RESEARCH DESIGN AND METHODS This study included consecutive patients with diabetes and ACS between January 2015 and November 2016. GV was assessed using SD during initial hospitalization. MACE, including new-onset myocardial infarction, acute heart failure, and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analyzed with respect to baseline characteristics and cardiac status. RESULTS A total of 327 patients with diabetes and ACS were enrolled. MACE occurred in 89 patients (27.2%) during a mean follow-up of 16.9 months. During follow-up, 24 patients (7.3%) died of cardiac causes, 35 (10.7%) had new-onset myocardial infarction, and 30 (9.2%) were hospitalized for acute heart failure. Multivariable logistic regression analysis showed that GV >2.70 mmol/L, a Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score >34, and reduced left ventricular ejection fraction of <40% were independent predictors of MACE, with odds ratios (ORs) of 2.21 (95% CI 1.64–2.98; P < 0.001), 1.88 (1.26–2.82; P = 0.002), and 1.71 (1.14–2.54; P = 0.009), respectively, whereas a Global Registry of Acute Coronary Events (GRACE) risk score >140 was not (OR 1.07 [0.77–1.49]; P = 0.69). CONCLUSIONS A GV cutoff value of >2.70 mmol/L was the strongest independent predictive factor for midterm MACE in patients with diabetes and ACS.Read less <