To assess the diagnostic accuracy of ventilation/perfusion (V/Q) single photon emission CT (SPECT) as compared to computed tomographic pulmonary angiography (CTPA) for pulmonary embolism (PE). In this prospective multicenter study, 111 patients in whom acute or sub-acute PE was clinically confirmed or suspected were enrolled. The patients underwent one-day method V/Q lung scan (including SPECT and planar imaging) within 3 days before and after completion of CTPA. The European Association of Nuclear Medicine (EANM) guidelines for ventilation/perfusion scintigraphy (2009) reference was used as the evaluation criteria of V/Q SPECT imaging. The refined modified prospective investigation of pulmonary embolism diagnosis (RM-PIOPED) criteria was used for evaluation of planar imaging. According to the direct and indirect signs of PE, the imaging of CTPA was evaluated. All patients were followed for at least 6 months. A diagnosis was finally made by consensus of respiratory physicians, radiologists and nuclear medicine physicians based on the clinical data, laboratory tests, imaging features and follow-up results. The difference among diagnostic methods was evaluated for significance using chi-square test. The receiver operator characteristic (ROC) curve was drawn according to the results of the 3 diagnostic tests. The area under ROC curve (AUC) was calculated and compared. P < 0.05 was considered statistically significant. Among the 111 patients, PE was confirmed in 80, and excluded in 31. The diagnostic sensitivity/specificity/accuracy of V/Q SPECT, planar imaging, and CTPA were 85.9%/93.5%/88.1%, 75.7%/92.9%/81.4%, and 85.5%/90.0%/86.8%, respectively. By ROC curve analysis, the AUC values of V/Q SPECT, planar imaging and CTPA were 0.898, 0.838, and 0.877, respectively; with 95% confidence intervals [CI] 0.831 to 0.966, 0.759 to 0.917, and 0.801 to 0.954, respectively. The area of the fitted smooth ROC curve was statistically significant (P < 0.05) as compared with the area under the reference line. The results indicate that SPECT V/Q imaging is superior to V/Q planar scan and CTPA in the diagnosis of PE.