['To investigate the diagnostic performance of perfusion single-photon emission computed tomography/computed tomography (Q-SPECT/CT) in patients suspected to have pulmonary embolism (PE) but with indeterminate computed tomographic pulmonary angiography (CTPA) or planar ventilation/perfusion (V/Q) scans.', 'This retrospective study included two groups of patients. Group I consisted of 49 patients with nondiagnostic CTPA. These 49 patients underwent subsequent V/Q scans. Further Q-SPECTs were obtained in patients with indeterminate planar images and fused with existing CTPA. Group II consisted of 182 non-CTPA patients with indeterminate V/Q scans. These 182 patients underwent further Q-SPECT and separate noncontrast low-dose CT chest. Fusion Q-SPECT/CT scans were obtained through FDA-approved software and interpreted according to published criteria as positive, negative, or indeterminate for PE. Upon retrospective analyses, the final diagnosis was made using composite reference standards including all available clinical and imaging information for at least 6-month follow-up.', 'In group I patients, 1 was positive, 24 were negative, and another 24 (49\xa0%, 24/49) were indeterminate. In the subsequent 24 Q-SPECT/CTPAs, 4 were positive, 19 were negative, and 1 was indeterminate (4.2\xa0%, 1/24). In group II patients, 9 (4.9\xa0%, 9/182) were indeterminate, 33 were positive, and 140 were negative. The combined nondiagnostic rate for Q-SPECT/CT was only 4.9\xa0% (10/206). There was six false-negative and one false-positive Q-SPECT/CT examinations. The sensitivity, specificity, and positive and negative predictive value of Q-SPECT/CT were 85.7\xa0% (36/42), 99.4\xa0% (153/154), 97.3\xa0% (36/37) and 96.2\xa0% (153/159), respectively.'] Does software-Based Hybrid Perfusion SPECT/CT provide Diagnostic Accuracy When Other Pulmonary Embolism Imaging Is Indeterminate?