Hypertensive patients have a younger trend, and studies on the role of genetic factors in hypertension susceptibility have been inconsistent. Aldehyde dehydrogenases 2 (ALDH2) and apolipoprotein E (APOE) are involved in the pathophysiological processes of hypertension. To investigate the relationship of ALDH2 and APOE polymorphisms with hypertension in middle-aged (30-59 years old) and elderly (≥60 years old) persons. Two thousand six hundred and ten hypertensive patients and 1921 controls were included (between 30 and 100 years old). The genotypes of common polymorphisms in APOE and ALDH2 genes (APOE rs429358, rs7412, and ALDH2 rs671) of the subjects were analyzed by polymerase-chain reaction (PCR)-microarray. Statistical analyses (Student's t-test, Mann-Whitney U-test, χ 2 test, and logistic regression analysis) were performed with SPSS v21.0. There were 4531 participants (66.60 ± 12.10 years old) in this study, including 3057 (67.5%) males and 1474 (32.5%) females. There were no significant differences in distributions of ALDH2 rs671, APOE rs429358/rs7412 genotypes and alleles between hypertensive patients and controls. Persons with ALDH2 rs671 G/A or A/A genotype were less likely to have hypertension (G/A+A/A vs G/G: gender-, age-, smoking-, and drinking-adjusted OR 0.885, 95% CI 0.785-0.997, P=0.045), while ALDH2 rs671 A/A+APOE rs429358 or rs7412 wild-type genotype may decrease the risk of hypertension. In middle-aged group, ALDH2 rs671 G/A+APOE rs429358 T/C carriers (adjusted OR 0.547, 95% CI 0.350-0.856, P=0.008), and ALDH2 rs671 A/A+APOE rs7412 C/C genotypes (adjusted OR 0.567, 95% CI 0.361-0.891, P=0.014) were less likely to have hypertension. In elderly group, APOE rs7412 T/T carriers were more likely to have hypertension (rs671 T/T vs C/C: adjusted OR 4.755, 95% CI 1.075-21.027, P=0.040; rs671 T/T vs C/C or C/T: adjusted OR 4.734, 95% CI 1.071-20.928, P=0.040). Polymorphism-polymorphism interactions of ALDH2 rs671 and APOE rs429358/rs7412 may effect on hypertension susceptibility. Different genotypes comparison shows different roles in middle-aged and elderly people, respectively.