Elastic registration of inspiratory and expiratory MRI revealed qualitative and quantitative differences in lung deformation in study participants with systemic sclerosis compared with healthy volunteers. Background Current imaging methods are not sensitive to changes in pulmonary function resulting from fibrosis. MRI with ultrashort echo time can be used to image the lung parenchyma and lung motion. Purpose To evaluate elastic registration of inspiratory-to-expiratory lung MRI for the assessment of pulmonary fibrosis in study participants with systemic sclerosis (SSc). Materials and Methods This prospective study was performed from September 2017 to March 2018 and recruited healthy volunteers and participants with SSc and high-resolution CT (within the previous 3 months) of the chest for lung MRI. Two breath-hold, coronal, three-dimensional, ultrashort–echo-time, gradient-echo sequences of the lungs were acquired after full inspiration and expiration with a 3.0-T unit. Images were registered from inspiration to expiration by using an elastic registration algorithm. Jacobian determinants were calculated from deformation fields and represented on color maps. Similarity between areas with marked shrinkage and logarithm of Jacobian determinants less than −0.15 were compared between healthy volunteers and study participants with SSc. Receiver operating characteristic curve analysis was performed to determine the best Dice similarity coefficient threshold for diagnosis of fibrosis. Results Sixteen participants with SSc (seven with pulmonary fibrosis at high-resolution CT) and 11 healthy volunteers were evaluated. Areas of marked shrinkage during expiration with logarithm of Jacobian determinants less than −0.15 were found in the posterior lung bases of healthy volunteers and in participants with SSc without fibrosis, but not in participants with fibrosis. The sensitivity and specificity of MRI for presence of fibrosis at high-resolution CT were 86% and 75%, respectively (area under the curve, 0.81; P = .04) by using a threshold of 0.36 for Dice similarity coefficient. Conclusion Elastic registration of inspiratory-to-expiratory MRI shows less lung base respiratory deformation in study participants with systemic sclerosis–related pulmonary fibrosis compared with participants without fibrosis.