On the basis of data from the Women's Health Initiative, Smoller et al report that antidepressant use is associated with an increased risk of stroke and all-cause mortality, but not coronary heart disease, in a study of 136 293 postmenopausal women with a mean follow-up of 5.9 years. Selective serotonin reuptake inhibitor (SSRI) use was associated with increased risk of stroke (hazard ratio [HR], 1.45) and all-cause mortality (HR, 1.32). In analyses by stroke type, SSRI use was associated with incident hemorrhagic (HR, 2.12) and fatal stroke (HR, 2.10). However, there were no significant differences between SSRI and tricyclic agent use in risk of cardiovascular event or mortality. The authors suggest that physicians should be vigilant about controlling other modifiable cardiovascular risk factors in older women taking antidepressants.