The WHO African region bears a disproportionate burden of morbidity and mortality related to chronic hepatitis B virus (HBV) infection and accounts for an estimated 70% of new HBV infections worldwide. We investigated the extent to which HBV clinical trials represented populations in this region by searching the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for interventional clinical trials published in English between database inception and May 29, 2023, using the search term "Hepatitis B". We identified 1804 unique clinical trials, of which 18 (1·0%) recorded involvement of the WHO African region. There is no evidence that the number of HBV clinical trials in this region has improved over time. The diversity of new interventions and industry sponsorship in the WHO African region were low, with trials of HBV comparing poorly with those of other endemic infectious diseases (eg, malaria, HIV, and SARS-CoV-2). HBV research and clinical trial investigations have neglected the WHO African region, leading to profound health inequities. HBV clinical trials are urgently needed to evaluate the efficacy of newly discovered therapeutics and to ensure that interventions can be equitably distributed and deployed as they become available.