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<jats:title>Abstract</jats:title> <jats:p>The aim of this paper is to optimally design the set of <jats:italic>b</jats:italic>-values for diffusion weighted MRI with the aim of precise estimation of intra-voxel incoherent motion (IVIM) parameters (<jats:italic>f</jats:italic> perfusion fraction, <jats:italic>D</jats:italic> <jats:sub> <jats:italic>s</jats:italic> </jats:sub> slow diffusion, <jats:italic>D</jats:italic> <jats:sub> <jats:italic>f</jats:italic> </jats:sub> fast diffusion) according to the model developed by Le Bihan. Previous studies have addressed the design in a Monte Carlo fashion; however, due to huge computation times, this approach is practical only for a limited number of values of the parameters (<jats:italic>local design</jats:italic>): however, as the parameters of a specific patient are not known <jats:italic>a priori</jats:italic>, it would be desirable to optimise <jats:italic>b</jats:italic>-values over a <jats:italic>region</jats:italic> of parameters. In order to address this issue, we propose to use a D-optimal design approach. Our study has two key results: first, under fairy general conditions, the optimal design does not depend on perfusion fraction: this allow to perform a search over a 2D parameter space instead of 3D; second, as an exhaustive search over all possible designs would still be time consuming, we proposed an algorithm to find an approximate solution very quickly.</jats:p>