The relationship between apolipoprotein E (ApoE) and clinical manifestations of mild cognitive impairment (MCI) has not been investigated in non-Caucasian populations. This prospective study was conducted in an ethnic Chinese population to evaluate the correlations of ApoE genotype, cognitive performance, medial temporal structure volumes, and clinical outcome in amnestic MCI. Twenty normal elders, 58 MCI, and 20 mild Alzheimer's disease (AD) patients received neuropsychological, MRI, and ApoE genotype assessments at baseline. Patients with MCI had intermediate cognitive performance and hippocampal volumes between those in normal and AD groups. In each diagnostic group, epsilon4 carriers (E4+) consistently had smaller hippocampal volume than non-carriers (E4-) did. Nineteen MCI subjects (32.7%) converted to AD during the 3-year study period. Compared with MCI non-converters and E4- MCI converters, E4+ MCI converters had the smallest hippocampal volume. However, epsilon4 was not a predictor for AD. Both cognitive performance and hippocampal volume were predictive for progression to AD. However, stepwise Cox regression model integrating both neuropsychological and radiological variables showed that global cognitive performance was the only significant predictor for AD. A poor global cognitive score may be more crucial than a small hippocampal volume in the prediction of AD.