Previous longitudinal cohort studies have suggested an association between baseline depressive symptoms and incident hypertension. We assessed this possible association using data from the Multi-ethnic Study of Atherosclerosis, a population-based prospective cohort study of 6814 US adults from 4 different racial/ethnic groups. Baseline users of antihypertensive medications and participants lost to follow-up were excluded leaving 3914 participants. Patients with baseline depressive symptoms (n=622) were defined using a high score on the Center for Epidemiological Studies Depression Scale (>or=16) or the use of an antidepressant medication. Hypertension was defined as systolic blood pressure of >or=140 mm Hg, diastolic blood pressure of >or=90 mm Hg or new use of antihypertensive medications plus physician diagnosis. Estimates were adjusted for known risk factors, including age, sex, baseline blood pressure, diabetes, and body mass index. Untreated blood pressure was estimated using an imputation approach. A total of 477 participants developed hypertension. Using relative risk regression, patients with baseline depressive symptoms did not have an increased risk of incident hypertension (relative risk: 1.02; 95% confidence interval [CI]: 0.99 to 1.05), although an association between tricyclic antidepressants and hypertension (relative risk: 1.20; 95% CI: 1.05 to 1.37) was observed in subgroup analysis. Depression, even after adjustment for covariates, was associated with small changes in systolic (+2.4 mm Hg; 95% CI: 0.2 to 4.7) and diastolic (+0.8 mm Hg; 95% CI: -0.6 to 2.3) blood pressures. Depressive symptoms may be associated with slight increases in blood pressure in this multiethnic cohort, but it is premature to conclude much without longer studies in other populations.