Summary. Background: Little is known about residual abnormalities after pulmonary embolism (PE). Objectives: To assess risk factors and the clinical significance of perfusion defects in patients with PE. Patients/Methods: Consecutive patients receiving at least 3 months of anticoagulant for an acute PE were included in a prospective cohort study. Ventilation/ perfusion lung scan, echocardiography, 6-min walk test, thrombophilia and hemostatic variables were performed 6-12 months after PE. Perfusion defect was defined as a perfusion defect in at least two segments. Results: Seventy-three out of 254 patients (29%) had perfusion defects during follow-up (median 12 months) and were more likely to have dyspnea, had a higher systolic pulmonary arterial pressure [39 mmHg (SD) (12) vs. 31 mmHg (8); P < 0.001] and walked a shorter distance during the 6-min walk test [374 m (122) vs. 427 m (99); P = 0.004]. Age [odds ratio (OR) 1.35; 95% confidence interval (CI), 1.11-1.63], the time interval between symptom onset and diagnosis (OR, 1.17; 95% CI, 1.04-1.31), pulmonary vascular obstruction at the onset of PE (OR, 1.34; 95% CI, 1.16-1.55) and previous venous thromboembolism (OR 2.06; 95% CI, 1.03-4.11) were independent predictors of perfusion defect after treatment of acute PE. Total tissue factor pathway inhibitor concentration was associated with perfusion defects. Conclusions: Perfusion defects are associated with an increase in pulmonary artery pressure (PAP) and functional limitation. Age, longer times between symptom onset and diagnosis, initial pulmonary vascular obstruction and previous venous thromboembolism were associated with perfusion defects.