Objective: To assess the pulmonary artery (PA) diastolic-occlusion (wedge) pressure gradient in patients with acute pulmonary embolism and to evaluate this variable's diagnostic utility. Design: Retrospective, clinical review. Setting: Intensive care and cardiac catheterization units of a university medical center. Interventions: None. Patients: A series of 19 acute pulmonary embolism patients with concurrent right heart catheterization. Control groups consisted of 19 age-, sex-, and heart rate-matched critically ill controls who also underwent right heart catheterization, eight patients suspected of having pulmonary embolism who had negative pulmonary angiography and concurrent right heart catheterization, and 255 patients with a primary diagnosis of coronary artery disease who underwent right heart catheterization at the time of left heart catheterization. Measurements and Main Results: Initial hemodynamics (systolic, diastolic, and mean systemic and pulmonary arterial pressures, occlusion pressure, PA diastolic-occlusion pressure gradient, cardiac output, systemic and pulmonary vascular resistances) were compared between cohorts. Other than differences in the PA diastolic-occlusion pressure gradients, no significant differences were identified between cohorts. Pulmonary embolism patients were found to have increased PA diastolic-occlusion pressure gradients (10 +/- 5 vs. 3 +/- 2 mm Hg for the critically ill controls [p < .0002], and 4 +/- 4 mm Hg for the coronary artery disease cohort [p < .0005]). However, no significant difference in PA diastolic-occlusion pressure gradient values was identified when patients with proven pulmonary embolism were compared with patients in whom pulmonary embolism was clinically suspected yet not confirmed by angiograms (10 +/- 9 mm Hg; NS). For three of 19 pulmonary embolism patients, no occlusion pressure could be obtained due to an inability to wedge the balloon tip; 13 of 16 patients had PA diastolic-occlusion pressure gradients of greater than or equal to 8 mm Hg. In the pulmonary embolism cohort, PA diastolic-occlusion pressure gradient correlated well with pulmonary vascular resistance (r(2) = .50; p < .05), but not with cardiac output or heart rate. Conclusion: In the large number of patients with right heart catheters in whom the question of pulmonary embolism is raised, an increased PA diastolic-occlusion pressure gradient (especially greater than or equal to 8 mm Hg) may provide a clue to the diagnosis of pulmonary embolism, but is not specific for this diagnosis.