Simultaneous multi-contrast imaging (SMC) can be used to combine acquisition of diffusion-weighted (DW) and T2*-weighted (T2*W) images into a single scan. Compared to conventional single-contrast imaging, SMC reduces the total scan time and improves image registration. However, saturation effects can reduce SNR and alter contrast. In this study, these effects are investigated in simulations, in phantoms, and in vivo. By using the results of this study to control saturation effects in SMC, the method enables rapid acquisition of distortion-matched, high-quality, well-registered DW and T2*W imaging, which could support rapid diagnosis and treatment of acute stroke.