OBJECTIVE There is interest in using dual-energy computed tomography (DECT) to evaluate organ function before and after radiation therapy (RT). The purpose of this study (trial identifier: NCT04863027) is to assess longitudinal changes in lung perfusion using iodine maps derived from DECT in patients with lung cancer treated with conventional or stereotactic RT. METHODS For 48 prospectively enrolled patients with lung cancer, a contrast-enhanced DECT using a dual-source CT simulator was acquired pretreatment and at 6 and 12 months posttreatment. Pulmonary functions tests (PFT) were obtained at baseline and at 6 and 12 months posttreatment. Iodine maps were extracted from the DECT images using a previously described 2-material decomposition framework. Longitudinal iodine maps were normalized using a reference region defined as all voxels with perfusion in the top 10% outside of the 5 Gy isodose volume. Normalized functional responses (NFR) were calculated for 3 dose ranges: <5, 5 to 20, and >20 Gy. Mixed model analysis was used to assess the correlation between dose metrics and NFR. Pearson correlation was used to assess if NFRs were correlated with PFT changes. RESULTS Out of the 48 patients, 21 (44%) were treated with stereotactic body RT and 27 (56%) were treated with conventionally fractionated intensity-modulated RT. Thirty-one out of these 48 patients were ultimately included in data analysis. It was found that NFR is linearly correlated with dose (P < .001) for both groups. The number of months elapsed post-RT was also found to correlate with NFR (P = .029), although this correlation was not observed for the stereotactic body RT subgroup. The NFR was not found to correlate with PFT changes. CONCLUSIONS DECT-derived iodine maps are a promising method for detailed anatomic evaluation of radiation effect on lung function, including potentially subclinical changes.