BACKGROUND: Human immunodeficiency virus clinical trials are increasingly being conducted in sub-Saharan Africa. There is a tension between the pressure to increase levels of research participation and the need to ensure informed consent and protection of participants' rights. Researchers need to be aware of the particular ethical issues that underpin Human immunodeficiency virus research conduct in low income settings. This necessitates hearing from those who have participated in research and who have direct experience of the research process. OBJECTIVES: This review aimed to synthesize and present the best available evidence in relation to Human immunodeficiency virus research participation in sub-Saharan Africa, based on the views and experiences of research participants. TYPES OF PARTICIPANTS: The review included studies whose participants were current or former adult Human immunodeficiency virus research participants from sub-Saharan African countries. PHENOMENON OF INTEREST: Views, experiences, attitudes, understandings, perceptions and perspectives of Human immunodeficiency virus research participants in sub-Saharan Africa. Types of studies: This review considered studies that focused on qualitative data, including, but not limited to, designs such as phenomenology, ethnography, grounded theory, action research and feminist research. SEARCH STRATEGY: A three-step search strategy was utilized. Seven databases (CINAHL, Ovid MEDLINE (R) 1946, ASSIA, PsychInfo, Web of Science, EMBASE, and African Index Medicus) were searched with no limitation to years of publication, followed by hand searching of reference lists. Only studies published in the English language were considered. METHODOLOGICAL QUALITY: Methodological quality was assessed using the Qualitative Assessment and Review Instrument developed by the Joanna Briggs Institute. DATA EXTRACTION: Qualitative findings were extracted using the Joanna Briggs Institute Qualitative Assessment and Review Instrument. DATA SYNTHESIS: Qualitative research findings were pooled using a pragmatic meta-aggregative approach and the Joanna Briggs Institute Qualitative Assessment and Review Instrument software. RESULTS: Twenty-one studies were included in the review. One hundred and thirty-six findings were extracted from included studies and clustered into 14 categories based on similarities in meaning. These were further synthesized into five synthesized findings, set out below; i) Individuals are motivated to participate in Human immunodeficiency virus research due to a range of perceived benefits for themselves and others. ii) Participation in research can be associated with considerable fear and uncertainty. iii) Participation in Human immunodeficiency virus research is strongly influenced by social relationships (e.g. support or disapproval of family or friends) and social-economic and domestic factors (such as time or finances). iv). The meanings of research programs and processes are constructed within a context of existing lay beliefs, experiences and social relations associated with Human immunodeficiency virus and biomedical interventions in general. This means that local people may understand research and its processes very differently to health professionals. v) Participants' research experiences and their continued participation in Human immunodeficiency virus research are influenced by the research clinic context and the nature of their interactions with research staff. CONCLUSIONS: Individuals are generally willing to participate in Human immunodeficiency virus research. However their understanding of the process can be limited, and the experience may may cause anxiety or have negative consequences. Furthermore longer-term participation may become problematic due to socio-economic pressure or social commitments. IMPLICATIONS FOR PRACTICE: The review suggests a need to develop better ways to explain research processes and to support participants, when/if they encounter problems. There is also a need to engage better with communities in order to educate them about HIV research programs. IMPLICATIONS FOR RESEARCH: All the included studies focused on experiences around research enrolment and participation (retention); however there is a complete evidence gap on experiences of trial closure.