Abstract Background The use of antiretroviral therapy (ART) is a core strategy proposed by the World Health Organization in preventing mother to child transmission (MTCT) of HIV. This systematic review aimed to examine the enablers and barriers of medication adherence among HIV positive pregnant women in sub-Saharan Africa. Methods We used the following keywords: HIV AND (Pregnancy OR Pregnant*) AND (PMTCT OR “PMTCT Cascade” OR “Vertical Transmission” OR “Mother-to-Child”) AND (Prevent OR Prevention) AND (HAART OR “Antiretroviral Therapy” OR “Triple Therapy”) AND (Retention OR Concordance OR Adherence OR Compliance) to conduct electronic searches in the following databases: MEDLINE Complete (1916-Dec 2017), Embase (1947-Dec 2017), Global Health (1910-Dec 2017) and CINAHL Complete (1937-Dec 2017). Of the four databases searched, 401 studies were identified with 44 meeting the inclusion criteria. Seven studies were added after searching reference lists of included articles, resulting in 51 articles in total. Results The review demonstrated that stigma, cost of transportation, food deprivation and a woman’s disclosure or non-disclosure of her HIV status to a partner, family and the community, could limit or define the extent of her adherence to prescribed antiretroviral drugs during pregnancy. Furthermore, the review indicated that knowledge of HIV status, either before or during pregnancy, was significantly associated with medication adherence. Women who knew their HIV status before pregnancy demonstrated good adherence while women who found out their HIV infection status during pregnancy were linked with non-adherence to ART. Conclusion This review revealed several barriers and enablers of adherence among pregnant women taking ART in sub-Saharan Africa. Major barriers included the fear of HIV infection status disclosure to partners and family members, stigma and discrimination. A major enabler of adherence in women taking ART was women’s knowledge of their HIV status prior to becoming pregnant. Enhanced effort is needed to facilitate women’s knowledge of their HIV status before pregnancy to enable disease acceptance and management, and to support pregnant women and her partner and family in dealing with fear, stigma and discrimination about HIV.