Chemical shift-based water/fat separation, like iterative decomposition of water and fat with echo asymmetry and least-squares estimation, has been proposed for quantifying intermuscular adipose tissue. An important confounding factor in iterative decomposition of water and fat with echo asymmetry and least-squares estimation-based intermuscular adipose tissue quantification is the large difference in T1 between muscle and fat, which can cause significant overestimation in the fat fraction. This T1 bias effect is usually reduced by using small flip angles. T1-correction can be performed by using at least two different flip angles and fitting for T1 of water and fat. In this work, a novel approach for the water/fat separation problem in a dual flip angle experiment is introduced and a new approach for the selection of the two flip angles, labeled as the unequal small flip angle approach, is developed, aiming to improve the noise efficiency of the T1-correction step relative to existing approaches. It is shown that the use of flip angles, selected such the muscle water signal is assumed to be T1-independent for the first flip angle and the fat signal is assumed to be T1-independent for the second flip angle, has superior noise performance to the use of equal small flip angles (no T1 estimation required) and the use of large flip angles (T1 estimation required). Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.