This study evaluated the differences in the relationship between APOE genotype, hippocampal volume, memory performance and conversion to Alzheimer's disease (AD) between men and women with Mild Cognitive Impairment (MCI). MRI and clinical data were analyzed from 193 subjects participating in a three year clinical trial of Donepezil and Vitamin E for the treatment of MCI. Compared to MCI subjects with no APOE-e4 alleles, women with one or two e4 alleles were found to have significantly reduced baseline hippocampal volume and performance on a delayed word recall task. Men only showed significant reductions when carrying two e4 alleles. When controlling for memory performance on delayed word recall the APOE-e4 affect on hippocampal volumes was attenuated in men, but remained significant in women. In addition, APOE genotype was found to have a significantly greater affect on conversion to AD in women than men.