Patients with a new pleural effusion are often sent for a ventilation-perfusion scan to exclude a pulmonary embolism. This retrospective study assessed the probability of pulmonary embolism when a pleural effusion and a perfusion defect of similar size are the only significant imaging abnormalities. In 451 reports of patients who were scanned for suspected pulmonary embolism, 53 had perfusion defects secondary to pleural effusion without other significant perfusion defects. Using pulmonary angiography, venography, analysis of pleural fluid, clinical course, and other radiographic and laboratory studies to establish the final diagnosis, only two patients had documented venous thrombotic disease: one had pulmonary emboli, the other thrombophlebitis. Lung scans having significant perfusion defects limited to pleural effusions and matching them in size have a low probability for pulmonary embolism.