BACKGROUND Longitudinal associations between depressive symptoms and blood pressure have been inconsistent. Most studies have examined incident hypertension as an outcome, and few have examined effect modification. METHODS This study examined moderating influences of sex and age on coincident trajectories of depressive symptoms and blood pressure among 2,087 participants from the Baltimore Longitudinal Study of Aging (aged 19-97 years; 53% men; 74% white). Participants underwent clinical blood pressure measurement and completed the Center for Epidemiological Studies-Depression (CES-D) scale on up to 14 occasions (mean = 3.8; SD = 2.6) over up to 29 years (mean = 7.8; SD = 6.4). CES-D was log-transformed (CES-D(log)) for analyses. RESULTS Mixed-effects regression revealed that prospective relations of CES-D(log) to diastolic blood pressure differed by age in women (b = 0.095; P = 0.001) but not men; greater CES-D(log) attenuated the expected age-related decline in diastolic blood pressure. Across all testing sessions, greater CES-D(log) was associated significantly with higher average systolic blood pressure for women (b = 2.238; P = 0.006) but not men. Age-stratified analyses showed that greater CES-D(log) was associated significantly with higher average systolic (b = 3.348; P = 0.02) and diastolic (b = 1.730; P < 0.03) blood pressure for older adults (≥58.8 years at first visit). In the younger age cohort, sex moderated the relation of CES-D(log) to systolic blood pressure (b = -3.563; P = 0.007); greater CES-D(log) in women, but lesser CES-D(log) in men, was associated with higher systolic blood pressure. CONCLUSIONS Results demonstrate sex and age differences in the relation between depressive symptoms and blood pressure. Findings suggest the potential importance of preventing, detecting, and lowering depressive symptoms to prevent hypertension among women and older adults.