Monte Carlo simulations were performed to determine whether the multicomponent T2 distribution of tissue can be estimated accurately from T2 decay data acquired in vivo. Simulated data were generated for white matter, fast twitch muscle, and breast tissue. The signal-to-noise ratio, number of data samples, and minimum echo time were varied from the experimental conditions currently achievable with MRI to those achievable for in vitro experiments. Data were fitted by a distribution of T2 values using the T2NNLS algorithm, and statistics characterizing the estimated T2 components were determined. Current MRI techniques were found to provide conditions insufficient for accurate multicomponent T2 analysis on a pixel-by-pixel basis. However, volume localization methods that measure T2 decay from a large volume of interest have potential for this analysis. These results illustrate a general framework for development of new techniques to measure T2 decay accurately in vivo.