Objective: To evaluate the impact of timing of postpartum depot medroxyprogesterone acetate (DMPA) initiation on breastfeeding and effective contraceptive use over 28 weeks. Methods: We enrolled antepartum (n=86) and postpartum (n=98) women planning DMPA use for postpartum contraception. Women became ineligible if they did not initiate breastfeeding, decided against DMPA, or refused randomization. Participants were randomized to receive DMPA either pre-discharge or delayed (in 4-6 weeks). We assessed breastfeeding and contraceptive use every 2-4 weeks, for 28 weeks. We conducted intent-to-treat and as-treated analyses, conservatively assuming all lost-to-follow-up stopped breastfeeding and contraceptive use. Results: Of 184 women enrolled, 79 were randomized to pre-discharge and 78 to delayed DMPA; 27 women became ineligible before randomization. Mean age of randomized women was 24.2 years; 46% (72/157) were primiparous. Five women did not receive DMPA pre-discharge as randomized; five randomized to delayed received DMPA pre-discharge. Twenty four women were lost-to-follow-up and three withdrew (12 pre-discharge, 15 delayed). In intent-to-treat analyses, breastfeeding (any or exclusive) was similar at all timepoints, with pre- discharge or delayed DMPA initiation. At 2 weeks postpartum, 48% (38/79) women in the pre-discharge group and 47% (37/78) in the delayed group reported exclusive breastfeeding (p>.99); at 28 weeks, 35% (28/79) and 32% (25/78) reported any breastfeeding (p=.74). As-treated analyses produced similar findings. At 28 weeks postpartum, use of DMPA or more effective contraception was similar between groups in both analyses. Conclusions: Providing postpartum women with DMPA at hospital discharge does not impact breastfeeding or contraception, suggesting that breastfeeding should not delay provision of postpartum DMPA.