In this paper we investigate the effect of single-shell q-space diffusion sampling strategies and applicable multiple-fiber analysis methods on fiber orientation estimation in Diffusion MRI. Specifically, we develop a simulation based on an in-vivo data set and compare a two-compartment “ball-and-stick” model, a constrained spherical deconvolution approach, a generalized Fourier transform approach, and three related methods based on transforms of Fourier data on the sphere. We evaluate each method for N D 20, 30, 40, 60, 90 and 120 angular diffusion-weighted samples, at SNR D 18 and diffusion-weighting b D 1;000 s=mm2, common to clinical studies. Our results quantitatively show the methods are most distinguished from each other by their fiber detection ability. Overall, the “ball-and-stick” model and spherical deconvolution approach were found to perform best, yielding the least orientation error, and greatest detection rate of fibers.