Depot medroxyprogesterone acetate administered subcutaneously (DMPA-SC) is an all-in-one injectable contraceptive administered every 3 months, either by a trained health care provider or community health worker or by training a client to self-inject. Using a prospective cohort of family planning (FP) clients in Ghana, this study explores patterns of DMPA-SC use and mode of injection administration over a 6-month period. This study also examines the predictors of self-injection adoption 6 months after initiating DMPA-SC. Our analysis focuses on 378 women who were using DMPA-SC at the 6-month interview. Adjusted odds ratios accounting for clustering show that clients who were new FP users, never married, or attended high school/attained higher education were significantly more likely to self-inject by the third injection. Results of this study suggest that in Ghana, adding DMPA-SC to the method mix may improve access to FP, especially among new users. Results of this study may inform FP projects and programs aiming to improve access to contraceptive methods and increase contraceptive prevalence by introducing or scaling up DMPA-SC self-injection. The findings also provide a sociodemographic profile of FP clients most likely to adopt DMPA-SC self-injection over time, which could serve as an evidence base for social marketing strategies.