Depot-Medroxyl-Progesterone-Acetate-Subcutaneous/Self Injection (DMPA-SC/SI) is an intentional approach used by the Nigerian government to improve the coverage rate of contraceptives method-mix.  In this study, the knowledge, practice, and determinants of use of DMPA-SC/SI among women in North Central and South-West, Nigeria, was assessed. A cross-sectional health facility study was conducted across four Nigerian states. Structured pretested questionnaires were used to elicit information from 844 women within reproductive age. Twenty focused group discussions and 40 In-depth interviews

(IDIs). Descriptive statistics were used to analyze the characteristics of the women. Multivariate logistic regression was used to examine the determinants of the current use of DMPA-SC /SI. Statistical analyses were set at 5%. Recorded voices were transcribed in full and analyzed using literary methods.  About 89.5% of respondents reported ever heard family planning; 97.6% reported heard DMPA-SC; 83.2% reported ever use family planning; 95.7% reported current use of family planning; 94.3% reported ever use DMPA-SC, and 46.5% reported ever use DMPA-SC/SI. The reason for the use of DMPA-SC/SI was because it was easy to use, effective and self-administered. The factors that discourage women from using DMPA-SC/SI were mainly fears associated with side effects, for and fear of SI-self-injury. The logistic regression results showed that those residing in a rural part of the country were less likely to use DMPA-SC/SI. The government should scale up this model nationally, including rural and hard-to-reach communities with public awareness programmes, public sensitization, and refresher training to improve on Provider’s counselling skills.