Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary embolism (PE) is the third most common cardiovascular pathology after coronary artery disease and stroke with an incidence rate of 1 per 1000 individuals. Computed tomography pulmonary angiography (CTPA) as the gold standard examination in the detection of PE is contraindicated or unavailable in certain cases. Purpose The current study aimed to assess the accuracy of unenhanced CT in the diagnosis of PE. Methods A total of 195 consecutive participants with clinical suspicion for PE were enrolled in this prospective cohort study between October 2020 and March 2021. All patients were examined with a 16 slice multidetector (MD) CT scanner before performing the CTPA. Scans were independently reviewed by two expert radiologists who were blinded to patients’ clinical and laboratory history for imaging variables including presence and location of PE, hyper/hypodense intraluminal signs, pulmonary trunk enlargement, peripheral wedge-shaped opacity, and pleural effusion. First unenhanced CT scan and then CTPA were independently reviewed on a picture archiving and communications system workstation. Results There were 82 (42.1%) men and 113 (57.9%) women with the mean age ± standard deviation of 56 ±0.24 years. Based on CTPA results, 47 (24.1%) of 195 patients had PE of which 28 (59.5%) patients had central PE and 19 (40.5%) patients had peripheral PE. However, only 20 cases (42.5%) were detected with PE on MDCT scans consisting of 17 cases with (85%) central emboli and 3 cases with (15%) peripheral emboli. Given intraluminal clot density, 12 (60%) patients had hyperdense signs, 3 (15%) patients had hypodense signs, and 5 (25%) patients had mixed hyper-hypodense signs. There was a significant difference between central and peripheral embolies detected by MDCT. Intraluminal sign had the highest specificity and sensitivity (98.6%, 42.5%, AUC:0.734) followed by pulmonary trunk enlargement (84.4%, 36.1%, AUC: 0.603), peripheral wedge-shaped opacity (72.9%, 34%, AUC: 0.535), and pleural effusion (58.7%, 40.4%, AUC: 0.496). Our results did not show a remarkable difference in secondary findings from the MDCT scan including pulmonary trunk enlargement, peripheral wedge-shaped opacity, and pleural effusion concerning the presence of PE. Pleural effusion as the most common secondary finding in patients with PE was found in 31 (68.8%) of them. Conclusion Unenhanced MDCT has an acceptable performance to detect PE particularly central clots and should be considered as an alternative modality when CTPA is not available or indicated. Furthermore, the intraluminal sign is the main indicator of PE in MDCT images with the highest specificity and sensitivity. We recommend radiologists and other clinicians to be aware of intraluminal signs in case of unexpected PE.