Lateralization of memory by functional MRI (fMRI) may be helpful for surgical planning related to the medial temporal lobe (MTL). Most fMRI memory studies have calculated lateralization indices (LI) in the MTL from suprathreshold voxels only, but the selection of threshold remains highly arbitrary. We hypothesized that LIs could be reliably extracted from the distribution of voxels encompassing all positiveTstatistical values, each weighted by their own statistical significance. We also hypothesized that patient LIs that are two or more standard deviations (SD) away from the control group mean LI may be more clinically relevant than LIs that are not compared to control group. Thirteen healthy subjects had memory fMRI, and five epilepsy patients had both fMRI and the intracarotid amobarbital procedure (IAP). The fMRI task consisted of encoding patterns, scenes, and words. We found that normal subjects' LIs extracted from whole weighted statistical distributions tended to lateralize to the left for words, to the right for patterns, and intermediately for scenes, consistent with previous research. Weighted LIs were less variable than those calculated from suprathreshold voxels only. Using this approach, all patients had fMRI memory lateralizations consistent with IAP results. The weighted LIs provided a more clear-cut distinction of patients from the normal group (in terms of SDs from the group mean) than the suprathreshold voxel count approach. Our results suggest that using weighted distributions can be a useful strategy for assessing memory lateralization by fMRI in the MTL.