The present study compared blood pressure levels between subjects with clinical anxiety and depressive disorders with healthy controls. Cross-sectional data were obtained in a large cohort study, the Netherlands Study of Depression and Anxiety (N=2981). Participants were classified as controls (N=590) or currently or remittedly depressed or anxious subjects (N=2028), of which 1384 were not and 644 were using antidepressants. Regression analyses calculated the contributions of anxiety and depressive disorders and antidepressant use to diastolic and systolic blood pressures, after controlling for multiple covariates. Heart rate and heart rate variability measures were subsequently added to test whether effects of anxiety/depression or medication were mediated by vagal control over the heart. Higher mean diastolic blood pressure was found among the current anxious subjects (β=0.932; P=0.03), although anxiety was not significantly related to hypertension risk. Remitted and current depressed subjects had a lower mean systolic blood pressure (β=−1.74, P=0.04 and β=−2.35, P=0.004, respectively) and were significantly less likely to have isolated systolic hypertension than controls. Users of tricyclic antidepressants had higher mean systolic and diastolic blood pressures and were more likely to have hypertension stage 1 (odds ratio: 1.90; 95% CI: 0.94 to 3.84; P=0.07) and stage 2 (odds ratio: 3.19; 95% CI: 1.35 to 7.59; P=0.008). Users of noradrenergic and serotonergic working antidepressants were more likely to have hypertension stage 1. This study shows that depressive disorder is associated with low systolic blood pressure and less hypertension, whereas the use of certain antidepressants is associated with both high diastolic and systolic blood pressures and hypertension.