Purpose Whole-body MRI is seeing increasing use in the study and diagnosis of disease progression. In this, a central task is the visual assessment of the progressive changes that occur between two whole-body MRI datasets, taken at baseline and follow-up. Current radiological workflow for this consists in manual search of each organ of interest on both scans, usually on multiple data channels, for further visual comparison. Large size of datasets, significant posture differences, and changes in patient anatomy turn manual matching in an extremely labor-intensive task that requires from radiologists high concentration for long period of time. This strongly limits the productivity and increases risk of underdiagnosis. Materials and methods We present a novel approach to the comparative visual analysis of whole-body MRI follow-up data. Our method is based on interactive derivation of locally rigid transforms from a pre-computed whole-body deformable registration. Using this approach, baseline and follow-up slices can be interactively matched with a single mouse click in the anatomical region of interest. In addition to the synchronized side-by-side baseline and matched follow-up slices, we have integrated four techniques to further facilitate the visual comparison of the two datasets: the “deformation sphere”, the color fusion view, the magic lens, and a set of uncertainty iso-contours around the current region of interest. Results We have applied our method to the study of cancerous bone lesions over time in patients with Kahler’s disease. During these studies, the radiologist carefully visually examines a large number of anatomical sites for changes. Our interactive locally rigid matching approach was found helpful in localization of cancerous lesions and visual assessment of changes between different scans. Furthermore, each of the features integrated in our software was separately evaluated by the experts. Conclusion We demonstrated how our method significantly facilitates examination of whole-body MR datasets in follow-up studies by enabling the rapid interactive matching of regions of interest and by the explicit visualization of change.