No data is so far available on the relation between glucose values and insulin resistance and mortality, both at short- and long-term, in patients with acute heart failure syndromes (AHF). We prospectively assessed in 100 consecutive non-diabetic AHF patients whether acute glucose metabolism, as indicated by fasting glycemia and insulin resistance (HOMA index) was able to affect short- and long-term mortality. In the overall population, 51 patients showed admission glucose values >140 mg/dl. No significant difference was observed in admission and peak glycemia, insulin and C-peptide values and in HOMA-index between dead and survived patients. At multivariate logistic backward stepwise analysis the following variables were independent predictors for in-ICCU mortality (when adjusted for left ventricular ejection fraction): Fibrinogen (1 mg/dl increase) [OR (95% CI) 0.991 (0.984–0.997); p = 0.004]; NT-pro BNP (100 UI increase) [OR (95%CI) 1.005 (1.002–1.009); p = 0.004]; leukocyte count (1,000/μl increase) [OR (95%CI) 1.252 (1.070–1.464); p = 0.005]. eGFR was independently correlated with long-term mortality (HR 0.96, 95%CI 0.94–0.98, p < 0.001). In consecutive patients with acute heart failure without previously known diabetes, we documented, for the first time, that fasting glucose and insulin values and insulin resistance do not affect mortality at short- and long-term. Inflammatory activation (as indicated by the leukocyte count and the fibrinogen) and NT-pro BNP levels are independent predictors for early death while the eGFR affects the long-term mortality.