:Abstract Purpose: To compare the quantitative and qualitative lung perfusion data acquired with dual energy CT (DECT) to that acquired with a large field-of-view cadmium-zinc-telluride camera single-photon emission CT coupled to a CT system (SPECT-CT). Materials and methods: A total of 53 patients who underwent both dual-layer DECT angiography and perfusion SPECT-CT for pulmonary hypertension or pre-operative lobar resection surgery were retrospectively included. There were 30 men and 23 women with a mean age of 65.4 +/- 17.5 (SD) years (range: 18-88 years). Relative lobar perfusion was calculated by dividing the amount (of radiotracer or iodinated contrast agent) per lobe by the total amount in both lungs. Linear regression, Bland-Altman analysis, and Pearson's correlation coefficient were also calculated. Kappa test was used to test agreements in morphology and seventy of perfusion defects assessed on SPECT-CT and on DECT iodine maps with a one-month interval. Wilcoxon rank sum test was used to compare the sharpness of perfusion defects and radiation dose among modalities. Results: Strong correlations for relative lobar perfusion using linear regression analysis and Pearson's correlation coefficient (r = 0.93) were found. Bland-Altman analysis revealed a -0.10 bias, with limits of agreement between [-6.01; 5.81]. With respect to SPECT- CT as standard of reference, the sensitivity, specificity, PPV, NPV, accuracy for lobar perfusion defects were 89.4% (95% 'CI: 82.6-93.4%), 96.5% (95% CI: 92.1-98.5%), 95.6% (95% CI: '90.9-97.8%), 91.4% (95% CI: 85.6-94.9%) and 93.0% (95% CI: '87.6-96.1%) respectively. High level of agreement was found for morphology and severity of perfusion defects between modalities (Kappa =0.84 and 0.86 respectively) and on DECT images among readers (Kappa = 0.94 and 0.89 respectively). A significantly sharper delineation of perfusion defects was found on DECT images (P < 0.0001) using a significantly lower equivalent dose of 4.1 +/- 2.3 (SD) mSv (range: 1.9-11.85 mSv) compared to an equivalent dose of 5.3 +/- 1.1 (SD) mSv (range: 2.8-7.3 mSv) for SPECT-CT, corresponding to a 21.2% dose reduction (P = 0.0004). Conclusion: DECT imaging shows strong quantitative correlations and qualitative agreements with SPECT-CT for the evaluation of lung perfusion.