Objectives: To evaluate the effects of interactions between ApoE genotypes, alcohol consumption and obesity on the age-related trends of blood pressure (BP) levels in postmenopausal women. Study design: A population-based prospective cohort study of all residents in Bambuì, south-eastern Brazil, aged 60 years or older. Repeated BP measurements were obtained in four waves from 851 women who underwent ApoE genotyping at baseline (88.3% of those enrolled), and multi-level random-effects pattern-mixture models were used to evaluate the age-related BP trajectories, while accounting for non-ignorable dropouts/deaths and handling heterogeneities as random parameter variations. The few measurements (2.1%) made during hormone replacement therapy were excluded from the analysis. Results: Alcohol consumption was associated with high levels of systolic and diastolic BP in an age × genotype-dependent manner only in the non-obese women (BMI < 27 kg/m2). Among those with the ɛ3/3 genotype, the differences in systolic and diastolic levels between drinkers and non-drinkers estimated at the age of 60 years were respectively 13.7 mmHg (p = 0.022) and 10.7 mmHg (p = 0.002), and disappeared in the older age groups, in which drinking was associated with systolic/diastolic hypertension if the non-obese women were ɛ4 carriers. Conclusion: In non-obese postmenopausal women, alcohol consumption is associated with systolic and diastolic hypertension early in those with the ɛ3/3 ApoE genotype, and late in ɛ4 carriers. We hypothesize the mediation of androgen hormones and the influence of ApoE genotypes on age at natural menopause. A better understanding of these mechanisms may guide better preventive choices.