High resolution volume coverage of the brain in fMRI studies can be accomplished using multi-slice, multi-shot EPI. We demonstrate that the optimum contrast sensitivity in BOLD based fMRI experiments using multi-shot EPI is achieved by using the shortest possible TR values between segments and the longest tolerable echo train length. For a fixed paradigm time, acquiring the largest number of images under these conditions yields the best statistical detection thresholds. For a multi-slice multi-shot EPI fMRI study, the best approach is to perform the acquisition of all the segments in a single slice before continuing on to each of the slices in turn. Our results regarding the number of shots and TR are also applicable to other multi-shot techniques such as interleaved spirals.