To describe women's experiences with subcutaneous depot medroxyprogesterone acetate (DMPA-SC) to inform scale-up of self-administered DMPA-SC.We conducted a 12-month randomized controlled trial in Malawi to measure DMPA-SC continuation rates. A total of 731 women presenting at six Ministry of Health clinics or to community health workers (CHWs) in rural communities were randomized to receive DMPA-SC administered by a provider or be trained to self-inject DMPA-SC. Data collectors contacted women after the reinjection window at 3, 6 and 9 months to collect data on satisfaction and use; self-injectors were also queried about storage and disposal of DMPA-SC. We compared frequencies of injection experiences and satisfaction by study group and over time.Ninety-two percent of women who self-injected felt it was easy to do the first time. Women in the self-administered group primarily gave themselves the injection versus having someone else inject them; stored DMPA-SC mostly in bags, often in ways to keep the product away from others; and properly disposed of DMPA-SC in pit latrines. Women in both groups used printed calendars to remember when to get/be given their next injection. Both groups reported high satisfaction with DMPA-SC.Women in low-resource settings can be successfully trained by public sector CHWs and clinic-based providers to self-inject and to appropriately store and dispose of DMPA-SC. DMPA-SC and self-injection are acceptable and feasible in a low-resource setting.Self-administered and provider-administrated DMPA-SC should be scaled up, and the lessons learned during our trial should be applied to future scale-up efforts.