OBJECTIVE: The purpose of this study was to examine the diagnostic efficacy of hippocampal volumetry and the Mini-Mental State Examination (MMSE) in differentiating amnestic mild cognitive impairment from the normal changes of aging. SUBJECTS AND METHODS: The conditions of healthy older persons (n = 17) and persons with amnestic mild cognitive impairment (n = 18) were classified on the basis of results of comprehensive neuropsychological assessment. All subjects underwent MRI at 4 T, including high-resolution coronal T1-weighted images. Hippocampal volume was calculated by tracing right and left hippocampal formations on coronal slices and normalizing by single-slice intracranial area. Receiver operating characteristic analysis and logistic regression analysis were performed to evaluate the diagnostic efficacy of hippocampal volume and the MMSE in differentiating subjects with amnestic mild cognitive impairment from subjects with normal cognitive function. RESULTS: The mean +/- SE area under the receiver operating characteristics curve (AUC) for left hippocampal volume (0.886 +/- 0.056) was greater than that for right hippocampal volume (0.614 +/- 0.097). The AUC for MMSE score (0.745 +/- 0.085) was intermediate and not statistically different from that of hippocampal volume measurements alone. The AUC for the combination of left hippocampal volume and MMSE score (0.92) was significantly greater than that of MMSE score alone (p < 0.05). CONCLUSION: In the diagnosis of amnestic mild cognitive impairment, use of left hippocampal volume may be more efficacious than use of right hippocampal volume and may add to the value of routine screening MMSE. Automated hippocampal volumetry may become a useful diagnostic adjunct in settings in which sophisticated neuropsychological testing is not readily available.