Background <p>The prevalence of hypertension in Sub-Saharan Africa is as high as 48%, with medication adherence as low as 34.1%. Prioritizing hypertension management through medication adherence is the most effective means to improve outcomes. We report a systematic review of evidence-based interventions for medication adherence that, when effectively implemented, can improve hypertension management in Sub-Saharan Africa.</p> Methods <p>We searched the Web of Science, CINAHL, EMBASE, Global Index Medicus, PubMed/Medline, and APA PsycINFO databases. The search included articles from inception to October 26, 2022, which was later updated on October 1, 2023. Only studies (randomized controlled trials (RCTs), Non- RCTs, and Mixed Methods studies) conducted in Sub-Saharan Africa that reported on interventions addressing hypertension management and medication adherence, and reported on implementation outcomes, were included. The studies were assessed and categorized according to the standard of the framework developed by Proctor E, et al. and the scalability element developed by Gyamfi J, et al. The implementation outcomes assessed included acceptability, adoption (uptake), appropriateness, cost, feasibility fidelity, penetration, scalability, and sustainability. An Assessment of quality and risk of bias for each study was performed by two reviewers using the Cochrane risk-of-bias tool (RCTs), the JBI Critical Appraisal Tool for Quasi-Experimental Studies (Non-RCTs) and the Mixed Methods Appraisal Tool for all other study types.</p> Results <p>A total of 3,782 articles were identified through database and citation searches. After removing duplicates and article screening, 14 articles met all of the study’s inclusion criteria and were extracted. The studies included were implemented in Nigeria, Uganda, Ghana, and South Africa. Pharmacist-led (<i>n</i> = 4), Nurse-led (<i>n</i> = 2), Mobile (<i>n</i> = 3), Group (<i>n</i> = 2), and Health education (<i>n</i> = 3) interventions were included. All 14 interventions demonstrated improvements in medication adherence. Among studies reporting both pre and post intervention data, improvements ranged from 1.3 to 88%. The implementation outcomes measured helped to clarify how practitioners can implement these evidence-based interventions more effectively. The implementation outcomes of appropriateness, feasibility, acceptability, and cost were identified in more than half of the studies.</p> Conclusions <p>The implementation of evidence-based hypertension interventions can improve medication adherence. However, stakeholder input and further research is needed to assess the practicality of implementing evidence-based intervention in Sub-Saharan Africa.</p> Protocol Registration <p>This review was registered with PROSPERO (CRD42023360315). <a href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023360315">https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023360315</a>.</p>