Objectives: Patients with acute heart failure (AHF) often receive initial non-invasive ventilation (NIV). This study aimed to evaluate the prognostic role of NIV in patients hospitalized for AHF. Methods: This was a retrospective cohort study. We enrolled patients admitted to our cardiac intensive care unit with a diagnosis of AHF. Anthropometric, clinical, pharmacological, and instrumental assessments were collected. Both in-hospital and 180-day post-discharge mortality were evaluated. Results: Among 200 patients (mean age 81 ± 9 years; 52% male), NIV was applied in 80 cases (40%). These patients had more severe NYHA functional class, a higher prevalence of de novo AHF, required higher diuretic doses, and had longer hospital stays. In multivariate analysis, NIV remained significantly associated with length of stay (LOS) (r = 0.26; p = 0.0004). In-hospital mortality was 5% overall and significantly higher in the NIV group compared to non-NIV patients (10% vs. 1.6%, p < 0.001). At 180 days, mortality was also significantly higher in the NIV group [hazard ratio (HR) 1.84; 95% confidence interval (CI): 1.18–2.85; p = 0.006]. After adjusting for age, BNP, CRP, arterial blood gas parameters, renal function, and LVEF, NIV remained an independent predictor of 180-day mortality (HR 1.61; 95% CI: 1.01–2.54; p = 0.04). Conclusions: Patients with AHF who required NIV exhibited more severe disease and longer hospital stays. NIV use was independently associated with both in-hospital and post-discharge mortality, suggesting its potential role as a prognostic marker in AHF.