Objective The purpose of this study was to investigate the value of left atrial (LA) volume and strain by 4D auto left atrial quantification (LAQ) for differentiating pre- and post-capillary pulmonary hypertension (PH), and compare the discriminative ability with echocardiographic pulmonary to left atrial global strain ratio (ePLAGS). Methods A total of ninety-eight subjects screened for intermediate to high probability of PH were prospectively enrolled in this study. Clinical history and laboratory data of all the patients were collected. All the patients underwent comprehensive transthoracic echocardiography and then LA volume and strain were measured by dedicated commercial software specially designed for LA 4D analysis. Results According to pulmonary arterial wedge pressure, the participants were divided into two groups: pre-capillary PH Group (n=39, age 53±24 year) and post-capillary PH Group (n=59, age 57 ± 18 year). LAVImax, LAVImin and LAVIpreA significantly increased, while LASr and LAScd obviously decreased in post-capillary PH group when comparing with pre-capillary PH group. Multivariate logistic regression analysis showed LAVImax (OR: 1.40; 95% CI, 1.05–1.87; P = 0.021) and LAScd (OR: 1.76; 95% CI, 1.18–2.49; P = 0.004) were powerful independent predictors for detecting post-capillary PH. The ROC analysis indicated that LAVImax (AUC=0.82, p < 0.001) and LAScd (AUC=0.78, p <0.001) had high discriminating power for predicting post-capillary PH groups, and their cutoff values were 35.69ml/m2 (sensitivity 86%, specificity 74%) and -9% (sensitivity 80%, specificity70%). Conclusions LAVImax and LAScd measured by 4D auto LAQ were powerful parameters for distinguishing pre-capillary PH from post-capillary PH.