Introduction: The score “H2FPEF’’ has been described as a tool to predict heart Failure with Preserved Ejection fraction (HFpEF). The scoring criteria and interpretation are as follows: 0 or 1, exclude HFpEF; 2-5, further examination is needed to confirm the diagnosis; and 6-9, high probability of HFpEF diagnosis. However, predicting the prognosis of patients by using this scoring system is an ongoing topic of interest. Hypothesis: H2FPEF score can be used to predict mortality and heart failure (HF) hospitalization in adults with normal left ventricular ejection fraction (LVEF) and dyspnea. Methods: We systematically searched Pubmed, Embase, and Scopus for abstracts and full-text articles from inception to May 2021. Studies were included if they evaluated the relationship between a high H2FPEF score (defined as ≥6) and mortality or hospitalization due to HF in adults with normal LVEF and/or dyspnea. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random-effects model by DerSimonian and Laird. Results: A total of 4 studies were included that had a total of 8071 patients (mean age: 72 years, 49% were females) with an overall mortality of 35%. The relationship between a high H2FPEF score between survivors and non-survivors demonstrated an association with mortality (OR:1.73 CI:1.41-2.11 p<0.01. Figure 1.). The association to mortality persisted in the subgroup analysis of patients who already had the diagnosis of HFpEF and in patients evaluated with unexplained dyspnea, (OR:1.55 CI:1.22-1.96 p<0.01. Figure 2.), (OR:2.02 CI:1.49-2.74 p<0.01 Figure 3.) respectively. In addition, a high H2FPEP was associated with HF related hospitalizations (OR:1.70 CI:1.26-2.29 p<0.01. Figure 4.). Conclusions: A high H2FPEF score is associated with mortality and HF hospitalization irrespective of the presence of a known HFpEF diagnosis. This could help identify a population that may warrant more aggressive monitoring and management strategies.