Metabolic syndrome (MetS) is reported to be associated with cognitive decline and dementia, in particular vascular dementia. However, the evidence linking MetS to Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), a precursor of AD, is inconsistent and limited. This study examined the association of MetS and its components with aMCI and how APOE-εe4 and younger age influenced this association. Participants with aMCI (n = 98) and cognitively normal controls (n = 802) were identified from baseline data in a second wave cohort of older subjects aged 55 and over in the Singapore Longitudinal Ageing Study-2 (SLAS-2) in 2009/2010. The associations of MetS and its individual components with aMCI were analyzed using logistic regression controlling for age, gender, education, current smoking, alcohol drink, leisure time activities score, Geriatric Depression Scale score, APOE-ε4, and heart disease or stroke. The analysis was repeated for associations stratified by age and APOE-ε4 status. In multivariate analysis, MetS was associated with an elevated risk of aMCI (OR = 1.79; 95% CI 1.15-2.77). Among MetS components, central obesity showed a significant association with aMCI (OR = 1.77; 95% CI 1.11-2.82). The association between MetS and aMCI remained significant on repeated analysis among subjects free of heart disease and stroke. This association was particularly stronger among participants with APOE-ε4 allele (OR = 3.35; 95% CI, 1.03-10.85) and younger (<65 years) participants with APOE-ε4 (OR = 6.57; 95% CI, 1.03-41.74). MetS was found to be associated with aMCI, especially in individuals with APOE-ε4 at younger age in this middle-aged and older cohort.