Background: Serotonin transporters have recently been described in bone, raising the possibility that medications that block serotonin reuptake could affect bone metabolism. Methods: We assessed current use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) and obtained serial bone mineral density (BMD) measurements in a cohort of 2722 older women (mean age, 78.5 years) participating in the Study of Osteoporotic Fractures, a prospective cohort study of community-dwelling women. Hip BMD was measured at the sixth examination and an average of 4.9 years later at the eighth examination. We categorized women as nonusers (used no SSRIs or TCAs at either examination; n=2406), SSRI users (used SSRIs but no TCAs at either examination; n=198), or TCA users (used TCAs but no SSRIs at either examination; n=118). Depressive symptoms were identified using a cutoff score of at least 6 on the Geriatric Depression Scale. Results: After adjustment for potential confounders, including the Geriatric Depression Scale score, mean total hip BMD decreased 0.47% per year in nonusers compared with 0.82% in SSRI users (P<.001) and 0.47% in TCA users (P=.99). Higher rates of bone loss were also observed at the 2 hip subregions for SSRI users. Results were not substantially altered when women who scored at least 6 on the Geriatric Depression Scale were excluded from the analysis. Conclusion: Use of SSRIs but not TCAs is associated with an increased rate of bone loss at the hip in this cohort of older women.