Background: Rectal cancer (RC) is a frequent malignancy for which magnetic resonance imaging (MRI) is the most common and accurate imaging. Iodine concentration (IC) can be quantified with spectral dual-layer computed tomography CT (DL-CT), which could improve imaging of RC, especially for evaluation of response to radiochemotherapy (RCT). Purpose: To compare a DL-CT system to MRI as the non-invasive imaging gold standard for imaging of RC to evaluate the possibility of a response evaluation with DL-CT. Material and Methods: Eleven patients who received DL-CT as well as MRI before and after RCT of RC were retrospectively included into this study. For each examination, a region of interest (ROI) was placed within the tumor. For MRI, the mean apparent diffusion coefficient (ADC) was assessed. For DL-CT, IC, z-effective, and Hounsfield Units (HU) were measured. IC, z-effective, and HU were normalized to the aorta. ADC was correlated to absolute and relative normalized IC, z-effective, and HU with Spearman's ρ. Differences before and after treatment were tested with Wilcoxon signed-rank test. Results: HU, IC, and Z-effective values in DL-CT images decreased significantly after RCT (P<0.01 for each comparison). The mean ADC increased significantly after RCT. Spearman's ρ of the absolute IC difference and the absolute ADC (both before and after RCT) is high and significant (ρ = 0.73; P = 0.01), whereas the ρ-value for z-effective (ρ = 0.56) or HU (ρ = 0.45) to ADC was lower and non-significant. Conclusion: Response evaluation of RC after RCT could be possible with DL-CT via the measurement of IC.