(1) Background: Hyperglycaemia and hypoglycaemia are both emerging risk factors for cardiovascular disease. Nevertheless, the potential effect of glycaemic variability (GV) on mid-term major cardiovascular events (MACE) in diabetic patients presenting with acute heart failure (AHF) remains unclear. This study investigates the prognostic value of GV in diabetic patients presenting with acute heart failure (AHF). (2) Methods: this was an observational study including consecutive patients with diabetes and AHF between January 2015 and November 2016. GV was calculated using standard deviation of glycaemia values during initial hospitalisation in the intensive cardiac care unit. MACE, including recurrent AHF, new-onset myocardial infarction, ischaemic stroke and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analysed with respect to baseline characteristics and cardiac status. (3) Results: In total, 392 patients with diabetes and AHF were enrolled. During follow-up (median (interquartile range) 29 (6–51) months), MACE occurred in 227 patients (57.9%). In total, 92 patients died of cardiac causes (23.5%), 107 were hospitalised for heart failure (27.3%), 19 had new-onset myocardial infarction (4.8%) and 9 (2.3%) had an ischaemic stroke. Multivariable logistic regression analysis showed that GV > 50 mg/dL (2.70 mmol/L), age > 75 years, reduced left ventricular ejection fraction (LVEF < 30%) and female gender were independent predictors of MACE: hazard ratios (HR) of 3.16 (2.25–4.43; p < 0.001), 1.54 (1.14–2.08; p = 0.005), 1.47 (1.06–2.07; p = 0.02) and 1.43 (1.05–1.94; p = 0.03), respectively. (4) Conclusions: among other well-known factors of HF, a GV cut-off value of >50 mg/dL was the strongest independent predictive factor for mid-term MACE in patients with diabetes and AHF.

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