Most diffusion imaging sequences rely on single-shot echoplanar imaging (EPI) for spatial encoding since it is the fastest acquisition available. However, it is sensitive to chemical-shift artifacts due to the low bandwidth in the phase-encoding direction, making fat suppression necessary. Often, spectral-selective RF pulses followed by gradient spoiling are used to selectively saturate the fat signal. This lengthens the acquisition time and increases the specific absorption rate (SAR). However, in pulse sequences that contain two slice-selective 180°refo-cusing pulses, the slice-selection gradient reversal (SSGR) method of fat suppression can be implemented; i.e., using sliceselection gradients of opposing polarity for the two refocusing pulses. We combined this method with the twice-refocused spin-echo sequence for diffusion encoding and tested its performance in both phantoms and in vivo. Unwanted fat signal was entirely suppressed with this method without affecting the water signal intensity or the slice profile. Magn Reson Med 60: 1256 -1260, 2008.