OBJECTIVE: To evaluate whether a 12-week home-based exercise program is more effective than usual care for alleviating depressive symptomology in the postpartum. METHODS: Eighty-eight women experiencing postpartum depressed mood were randomly assigned to a 12-week home-based exercise program or usual care. Outcomes assessed immediately post-treatment and 3-months post-treatment were the Hamilton Rating Scale for Depression (HAM-D) and Edinburgh Postnatal Depression Scale (EPDS). RESULTS: In the intention-to-treat analysis, the effect of the intervention on EPDS did not change from 3 to 6 months evaluations, but was modified by the baseline EPDS score, with subjects with greater depression at baseline (EPDS > 13) in the intervention group having a significantly lower postbaseline EPDS score compared with the usual care group (mean difference 4.06 points, 95%CI 1.51-6.61, p < 0.001). After adjusting for baseline HAM-D, subjects in the intervention group had a significantly lower HAM-D score at post-treatment compared with subjects in the usual care group (mean difference 1.83 points, 95%CI 0.24-3.41, p = 0.02). The difference in HAM-D became non-significant at 3-months post-treatment. CONCLUSIONS: Home-based exercise is a feasible nonpharmacological intervention with the potential to alleviate postpartum depressive symptoms, especially in women with higher initial depressed mood scores as measured by the EPDS. These findings may guide the design of future exercise clinical trials with postpartum depressed women.