Abstract. A 4D registration method for the spatio-temporal alignment of cardiac MR image sequences has been developed. The registration algorithm has the ability not only to correct any spatial misalignment between the image sequences but also any temporal misalignment which maybe the result of differences in the cardiac cycle between subjects and differences in the temporal acquisition parameters. The algorithm uses a 4D transformation model which is separated into a spatial and a temporal component: the spatial component is a 3D affine transformation which corrects for any misalignment between the two image sequences. The temporal component uses an affine transformation which corrects the temporal misalignment caused by differences in the initial acquisition offset and length of the two cardiac cycles. The method was applied to seven cardiac MR image sequences from healthy volunteers. The registration was qualitatively evaluated by visual inspection and quantitatively by measuring ...