BACKGROUND: Pulmonary embolism (PE) is a severe condition with nonspecific symptoms. Diagnosis relies on medical imaging but follow-up is currently based on clinical symptoms and general risk factors. The duration of anticoagulant treatment after an acute episode of PE is still subject to debate and the best method of identifying the risk of recurrence in individual patients is undefined. Tomographic lung scintigraphy ventilation/perfusion single photon emission computed tomography (V/P SPECT) has improved the diagnostic accuracy with regard to PE but has not been evaluated for PE follow-up. AIM: The aim of this prospective study was to quantitatively follow the natural history of treated PE using V/P SPECT, which could prove helpful in defining an anticoagulant treatment regime for individual patients. METHODS: Of 83 consecutive patients with clinically suspected PE examined with V/P SPECT, 23 patients with confirmed PE were followed by serial V/P SPECT examinations over a 6-month period. All patients were also followed clinically. RESULTS: The mean relative decrease in PE extent compared with the time of diagnosis was 54±26% at 2 weeks, 79±30% at 3 months, and 82±30% at 6 months. Significant resolution of mismatched perfusion defects occurred between V/P SPECT controls within the first 3 months of anticoagulation (P<0.001) but not thereafter. V/P SPECT identified four patients with chronic PE, even though all patients were free from symptoms at 3-month follow-up. CONCLUSION: Follow-up of PE with V/P SPECT is feasible to evaluate treatment effectiveness in individual patients and to identify patients that develop chronic PE. This study also confirms that resolution of perfusion defects after PE occurs within the first 3 months of treatment. It is therefore recommended that V/P SPECT follow-up should be considered at 3 months after diagnosis.