Objectives.  Personality factors parsimoniously capture the variation in dispositional characteristics that affect behaviours, but their value in predicting medication non‐adherence is unclear. We investigated the relationship between five‐factor model personality factors (Conscientiousness, Neuroticism, Agreeableness, Extraversion, and Openness) and medication non‐adherence among older participants during a six‐year randomized placebo‐controlled trial (RCT).Design.  Observational cohort data from 771 subjects aged ≥72 years enrolled in the Ginkgo Evaluation of Memory study, a RCT ofGinkgo bilobafor prevention of dementia.Methods.  Random effects logistic regression analyses examined effects of NEO Five‐Factor Inventory scores on medication non‐adherence, determined via pill counts every 6 months (median follow‐up 6.1 years) and defined as taking<80% of prescribed pills. Analyses adjusted for covariates linked with non‐adherence in prior studies.Results.  Each 5 year increment in participant age was associated with a 6.7% greater probability of non‐adherence (95% confidence interval, CI [2.4, 11.0]). Neuroticism was the only personality factor associated with non‐adherence: a 1SDincrease was associated with a 3.8% increase in the probability of non‐adherence (95% CI [0.4, 7.2]). Lower cognitive function was also associated with non‐adherence: a 1SDdecrease in mental status exam score was associated with a 3.0% increase in the probability of non‐adherence (95% CI [0.2, 5.9]).Conclusions.  Neuroticism was associated with medication non‐adherence over 6 years of follow‐up in a large sample of older RCT participants. Personality measurement in clinical and research settings might help to identify and guide interventions for older