Impairments in activities of daily living (ADL) are common after stroke and may be related to poststroke depression. We have demonstrated that remission of poststroke major depression was associated with improvement in ADL. The administration of antidepressants within the first 3 months after stroke has been shown to prevent poststroke depression, early administration might also improve recovery of ADL among patients with stroke. This study examines the effect of early versus late treatment with antidepressants on recovery in ADL. Among 62 patients after stroke, the therapeutic effect of a 3-month course of antidepressants begun during the first month after stroke was compared with the effect of treatment begun after 1 month. The severity of impairment was measured using the Functional Independence Measure (FIM) and post-treatment outcome was assessed over the following 21 months. Although both the early and late treatment groups showed improvements in FIM scores during the 3 months of treatment, the early treatment group improved significantly more than the late treatment group. After the treatment, the early treatment group maintained this improvement over 2 years while the late treatment group deteriorated over time. There were no significant differences in the 2 groups that would explain the findings. Recovery in ADL impairment after stroke appeared to be enhanced by the use of antidepressant medication if treatment was started within the first month after stroke. These findings are consistent with the hypothesis that there may be a time-related therapeutic window in the treatment of physical impairment associated with poststroke depression.