Extrapulmonary tuberculosis (EPTB) is common in HIV-infected patients, especially at lower CD4 cell counts, yet is often difficult to diagnose with certainty. A 35-year-old man presented with dyspnoea and constitutional symptoms of tuberculosis (TB). Laboratory investigations included a positive HIV test and a CD4 cell count of 138 cells/μL. Chest radiography revealed a globular-shaped heart and bilateral pleural effusions, while echocardiography confirmed a massive pericardial effusion. The new Xpert MTB/RIF (Xpert) assay detected rifampicin-sensitive Mycobacterium tuberculosis in pericardial as well as sputum samples. Smear of the pericardial sample was negative. The patient was started on anti-TB treatment and is presently well. He will initiate antiretroviral therapy after 4–6 weeks. To the best of our knowledge, this is the first case report of EPTB diagnosed on pericardial fluid using the Xpert assay in Africa. This report also summarises the use of this assay in the diagnosis of EPTB in HIV-associated TB.