Background: Soluble ST2 (sST2) has emerged as a powerful prognostic marker in chronic systolic heart failure with reduced ejection fraction (HFrEF). Elevated levels of sST2 are associated with adverse cardiac remodeling and fibrosis. However, few studies have investigated the relative prognostic value of sST2 collected from ambulatory patients with chronic heart failure with preserved ejection fraction (HFpEF) for long term outcomes. Hypothesis: We sought to determine the prognostic utility of a baseline sST2 partition value in the ambulatory setting as it related to risk for heart failure hospitalization and all-cause mortality. Methods: Single-center, retrospective observational study of subjects presenting to an ambulatory heart failure (HF) clinic from July 2014 to December 2016. Baseline sST2 levels were available for 156 subjects with stage C heart failure.. For purposes of this analysis in HFpEF, we excluded patients with EF ≤ 40% resulting in a study cohort of 73 subjects. The mean follow-up was 3.09 years ± 1.46 years. Analysis was performed with IBM SPSS Statistics 26. Discrete variables were expressed as counts (percentage) and were compared using the Chi-squared test. Mean differences of continuous variables were expressed as a mean ± standard deviation and compared using the unpaired Student’s t- test. The log-rank test (Mantel-Cox) was used to compare survival times on Kaplan-Meier curves. Results: Patients who had baseline sST2 ≥ 35 ng/ml were at increased risk for heart failure hospitalization (p=0.189) and all-cause mortality (p=0.073) compared to patients who had sST2 < 35 ng/ml. Patients with sST2 ≥ 35 ng/ml had a mean of 1.03 HF hospitalizations, 24.1% of this group had ≥ 2 HF hospitalizations and 17.2% all-cause mortality. Patients with sST2 < 35 ng/ml had a mean of 0.57 HF hospitalizations, 14.0% had ≥ 2 HF hospitalizations and 4.55% all-cause mortality. Conclusion: Subjects with sST2 levels ≥ 35 ng/ml were at increased risk of recurrent hospitalization and all-cause mortality. The results of this study highlight the value of sST2 concentrations as a prognostic biomarker for identifying patients with HFpEF that are at increased risk for morbidity and mortality in the ambulatory setting.