BACKGROUND: Planar ventilation/perfusion (V/Q) lung scintigraphy is a validated tool for the diagnosis of pulmonary embolism (PE). Nevertheless, given the high rate of nonconclusive V/Q, further investigation is often necessary. V/Q single-photon emission CT (SPECT) scan could improve V/Q performance, but sparse data are available on its accuracy. This study assessed the diagnostic performance of V/Q SPECT scan in a cohort of consecutive patients with suspected PE. METHODS: Three hundred twenty-one consecutive patients with a clinical suspicion of PE were prospectively included. Patients suspected of having PE were managed according to a reference diagnostic strategy validated by a 3-month follow-up. In addition to the reference strategy, patients had a V/Q SPECT scan, the results of which were compared with the initial work-up results. RESULTS: Prevalence of PE was 0 of 41 (0%; 95% CI, 0%-9%), six of 134 (4%; 95% CI, 2%-9%),15 of 36 (42%; 95% CI, 27%-58%), and 28 of 32 (88%; 95% CI, 72%-95%) in the normal, low,intermediate, and high V/Q SPECT scan probability groups, respectively. The combination of V/Q SPECT scan with clinical probability was diagnostic in 88% of patients. CONCLUSIONS: V/Q SPECT scan results show satisfactory accuracy for PE diagnosis. Validation of dedicated interpretation criteria is required, followed by outcome studies that use V/Q SPECT scan as part of a diagnostic strategy to rule out PE. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01183026; URL: www.clinicaltrials.gov