Although apolipoprotein E (ApoE) polymorphism is associated with variable risks of several illnesses, and with mortality, no persuasive relationship has been demonstrated with frailty. Here, the clinical examination cohort (n=1452 older adults, aged 70+ years at baseline) of the Canadian Study of Health and Aging was evaluated, with 5-year follow-up data. Frailty was defined using both the phenotypic definition from the Cardiovascular Health Study (Frailty-CHS) and the 'Frailty Index', from which age-specific trajectories of deficit accumulation can be estimated. In age-sex adjusted analyses, people with ApoE 4 allele had a higher risk of death (hazard ratio [HR]=1.20; 95% confidence interval: 1.01-1.45), but this relationship was not significant when adjusted for cognitive impairment (1.06; 95% confidence interval: 0.88-1.27). There was no association between frailty and ApoE polymorphism, defined in age-sex adjusted models either as Frailty-CHS (ApoE4 HR 1.17; 95% confidence interval: 0.98-1.40, frailty HR 1.37; 95% confidence interval: 1.28-1.46) or by the Frailty Index (ApoE4 HR 1.07; 95% confidence interval: 0.90-1.29, frailty HR 35.3; 95% confidence interval: 20.4-61.1). The data do not support an association between ApoE polymorphism and frailty. This result did not depend on how frailty was defined.