Background: Amnestic mild cognitive impairment (aMCI) is considered to be a prodromal stage of Alzheimer's disease. The clinical role of ischaemiamodified albumin (IMA) and the association between IMA and oxidative stress in aMCI have not been investigated. The aim of the study was to explore this relationship and to generate new ideas for controlling Alzheimer's disease. Methods: This community-based case-control study included 113 patients with aMCI and 832 cognitively normal controls. Serum levels of albumin and IMA, diacron-reactive oxygen metabolite, and biological anti-oxidant potential, were measured. The IMA/albumin ratio and the biological antioxidant potential/diacron-reactive oxygen metabolite ratio were calculated. Results: In univariate analysis, the serum IMA level and the IMA/albumin ratio were higher in the aMCI patients than in the controls (P < 0.001, P < 0.001, respectively). In multivariate analysis, a serum IMA level ≥476.4 ng/mL and an IMA/albumin ratio ≥9.4 were separately associated with the development of aMCI (odds ratio = 3.56, 95% confidence interval: 2.33-5.46; odds ratio = 3.43, 95% confidence interval: 2.25-5.27, respectively). There was a linear correlation between serum IMA level and several oxidative stress markers (biological anti-oxidant potential/diacron-reactive oxygen metabolite ratio: r = −0.585, P < 0.001; diacron-reactive oxygen metabolite: r = 0.549, P < 0.001; biological anti-oxidant potential: r = −0.293, P < 0.001). Conclusion: Serum IMA might be a potential biomarker for oxidative stress in aMCI.