Objective:This study explored the association of hypertension and psychiatric morbidity in patients with end-stage renal disease (ESRD) under adjusted personality characteristics and parental attachment. Methods: The mental health of 121 patients with ESRD in a general teaching hospital was evaluated using the 12-item version of the Chinese Health Questionnaire (CHQ). Only 40 males and 49 females completed all the questionnaires. Ten of the 40 males and 21 of the 49 females had high scores (≧4) and were allotted to the case group (n = 31). The remaining 58 patients constituted the control group (CHQ <4). Results: The logistic regression model showed that hypertension, gender, and neuroticism are statistically significant covariates. Hypertension, especially, was strongly associated with depressive vulnerability (odds ratio of hypertension versus without hypertension = 9.07:1). Structural equation modeling revealed that gender difference and hypertension directly influenced the individuals’ mental health status and that the influence of hypertension on mental health was highly variable. Conclusion:A parsimonious structural equation model provided considerable evidence that hypertension could have an important effect on depression in ESRD patients, when predisposing factors, such as personality characteristics and parental attachment, gender, duration of hemodialysis and other medical diseases were adjusted. Hence, hypertension might be a mediating factor of depressive vulnerability in ESRD patients underling genetic and environmental problems.