Background: Heart failure with preserved ejection fraction (HFpEF) has a high hospitalization rate. While recent guidelines recommend specific parameters like E/e’, e’ velocity, and left atrial volume index (LAVI) for diagnosing HFpEF, their clinical accuracy remains limited. Left atrial (LA) strain has emerged as a potential diagnostic parameter, yet its role in the Vietnamese population is unclear. This study aims to evaluate LA strain’s diagnostic role in HFpEF among Vietnamese patients, exploring its relationship with established parameters of left ventricle (LV) diastolic function to determine its potential utility as a diagnostic tool. Methods: A cross-sectional study was conducted from 15/04/2022 to 01/12/2023, involving 118 subjects, including 49 patients with HFpEF and 69 individuals without cardiac dysfunction. The study subjects were evaluated for LA strain and HFA-PEFF. Results: LA strain including LA reservoir (LASr), conduit (LAScd), and contractile (LASct) function, in the HFpEF group were 19.97% ± 9.18%, 9.08% ± 6.18%, and 10.89% ± 5.16%, respectively. The control group had corresponding LASr, LAScd, and LASct values of 34.70% ± 5.38%, 17.33% ± 5.72%, and 17.38% ± 4.41% (p < 0.001). The area under the curve (AUC) for LASr, LAScd, LAScr, HFA-PEFF, LAVI, and GLS to diagnose HFpEF was 0.877, 0.836, 0.749, 0.975, 0.587, and 0.717, respectively. Comparing the AUCs for diagnosing HFpEF between LASr and HFA-PEFF, no difference was found with p = 0.062. Conclusion: LA strain has a diagnostic value equivalent to the HFA-PEFF score in diagnosing HFpEF. These indices could be incorporated into the existing guidelines to enhance the diagnosis of HFpEF.