Chemical shift-based multipoint water-fat separation methods have been applied in balanced steady-state free precession (bSSFP) sequences because of the high signal-to-noise-ratio (SNR) attainable. In this approach the echo formation is approximated to occur concurrently for both water and fat at an echo time (TE) equal to half the repetition time (TR/2 approximation). However, the degree to which the imaging conditions underlying the TR/2 approximation are satisfied can significantly vary in vivo depending upon the imaging region of interest (ROI) and the pixels across a field of view (FOV). The consequence of the TR/2 approximation on chemical shift-based multipoint water-fat separation was investigated. The influence of a mismatch between the pass-band profiles of water and fat (pass-band mismatch) on fat quantification was also examined. Theoretical and experimental results demonstrate that the TR/2 approximation can result in spatially dependent noise performance of multipoint water-fat separation methods, and the pass-band mismatch can render the precision of fat quantification spatially dependent. Given that local tissue characteristics in affected liver can be substantially variable, this study is of particular importance in liver imaging.