Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging due to non-diagnostic imaging outputs and discordant clinical features. Using only a single videoclip from a standard transthoracic echocardiogram (TTE), we developed an artificial intelligence (AI) model to differentiate patients with HFpEF from those without HFpEF. In a separate test population, we assessed the model’s ability to predict cardiac mortality.Methods: A 3-dimensional convolutional neural network was developed and trained on apical 4-chamber videoclips to classify patients with HFpEF (cases) versus without HFpEF (controls). Overall and cardiac mortality were obtained from the National Death Index.Results: The model was independently tested in 646 cases and 638 controls from 8 centers in 4 states. Sensitivity (87.8%; 84.5-90.9%) and specificity (81.9%; 78.2-85.6%) were high and sustained in various subgroups, including increased left atrial volume index, average E/e’ ≥15, and pulmonary artery systolic pressure >35 mm Hg. During follow-up (median [IQR] 3.4 [1.7-6.5] years), 540 patients died. There were 135 cardiac deaths attributable to heart failure (47%), coronary artery disease (41%), valve disease (4%), arrhythmia (4%), and others (5%). Compared to a negative output, all-cause mortality was higher in patients with a positive (HR 2.9 [2.4-3.5]) or uncertain output (HR 1.8 [1.2-2.5]), and cardiac mortality (Figure) was also higher in patients with a positive (HR 7.7 [4.5-13.3]) or uncertain output (HR 3.4 [1.4-8.1]). Cardiac mortality differences according to AI model prediction remained after age adjustment (positive: HR 5.9 [3.3-10.4], p<0.001; uncertain: HR 2.8 [1.2-6.8], p=0.02).Conclusion: A novel AI model to detect HFpEF based on a single routinely acquired TTE videoclip also identifies those at increased risk of cardiac mortality.