AbstractThe degree of diffusion anisotropy in different brain regions is usually measured by a diffusion anisotropy index (DAI) such as relative anisotropy (RA) and fractional anisotropy (FA). FA has been reported to have a higher contrast‐to‐noise ratio (CNR) than RA. The present work compares the CNRs of seven DAIs in theoretical propagation‐of‐error calculations, in simulations, and in human brain measurements over small and large anisotropy differences. In simulations all seven CNRs were similar for small anisotropy differences. Small differences among the DAIs appeared at higher anisotropy levels and lower signal‐to‐noise ratios with certain tensor orientations. The DAIs fell into three groups based on algebraic relationships and small CNR differences. The group with RA and FA had the best CNR. Human brain regions with small anisotropy differences had similar CNR for all seven DAIs, and the scatter in the data was greater than any expected differences. With large anisotropy differences, a small advantage appeared for RA over FA in some simulations and for FA over RA in other simulations. The CNR between brain regions with very different anisotropies was different for each DAI. The apparent reported advantage of FA over RA is explained by biologic heterogeneity and by noise‐induced bias in the DAI values and their standard deviations. Magn Reson Med 53:911–918, 2005. © 2005 Wiley‐Liss, Inc.