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Background Pulmonary hypertension (PH) has diverse causes with heterogeneous physiology compelling distinct management. Differentiating patients with primarily elevated pulmonary vascular resistance (PVR) from those with PH predominantly due to elevated left sided filling pressure is critical. Methods and Results We reviewed hemodynamics, echocardiography, and clinical data for 108 patients seen at a referral PH clinic with transthoracic echocardiogram and right heart catheterization within 1 year. We derived a simple echocardiographic prediction rule to allow hemodynamic differentiation of PH due to pulmonary vascular disease (PHPVD, defined as pulmonary artery wedge pressure (PAWP) ≤ 15mmHg and PVR >3WU). Age averaged 61.3±14.8 years, μPAWP and PVR were 16.4±7.1mmHg and 6.3±4.0WU respectively, and 52 (48.1%) patients fulfilled PHPVD hemodynamic criteria. The derived prediction rule ranged from −2 to +2 with higher scores suggesting higher probability of PHPVD: +1 point for left atrial AP dimension<3.2cm; +1 for presence of a mid-systolic notch or acceleration time<80msec; −1 for lateral mitral E:e′>10; −1 for left atrial AP dimension>4.2cm. PVR increased stepwise with score (for −2, 0 and +2, μPVR were 2.5, 4.5, and 8.1WU) while the inverse was true for PAWP (corresponding μPAWP were 21.5, 16.5 and 10.4mmHg). Among subjects with complete data, the score had an AUC of 0.921 for PHPVD. A score ≥ 0 had 100% sensitivity and 69.3% positive predictive value for PHPVD, with 62.3% specificity. No patients with a negative score had PHPVD. Patients with a negative score and acceleration time >100msec had normal PVR (μPVR=1.8WU, range=0.7–3.2WU). Conclusions We present a simple echocardiographic prediction rule that accurately defines PH hemodynamics facilitates improved screening and focused clinical investigation for PH diagnosis and management.