Background Human immunoficiency virus (HIV)–associated pericardial effusion is common. We present its clinical features, cause, and prognosis on the basis of a review of 40 cases at a single public hospital. Methods A retrospective study was conducted of 122 patients with pericardial effusion (of which 40 were HIV associated) admitted to Queens Hospital Center from January 1988 to April 1997. A review of the literature is also presented. Results Forty patients with HIV-associated pericardial effusion represent 33% of the 122 patients with pericardial effusion admitted during that period. The most common symptom of the 40 patients was dyspnea (75%). Echocardiogram detected small effusions in 18 (45%), moderate effusions in 10 (25%), and large effusions in 12 (30%). Sixteen (40%) patients had cardiac tamponade, in 15 of whom pericardiocentesis or pericardiostomy was performed. Causes of cardiac tamponade were Mycobacterium species in 3 (19%), Streptococcus pneumoniae in 1 (6%), Staphylococcus aureus in 1 (6%), Kaposi’s sarcoma in 1 (6%), and unknown in 10 (63%). In comparison, causes of cardiac tamponade in 74 cases of acquired immunodeficiency syndrome in the literature were 45% idiopathic, 20% mycobacteria, 19% bacteria, 7% lymphoma, 5% Kaposi’s sarcoma, 3% viruses, and 1% fungus. Thirteen of the 40 patients were lost to follow-up. Among the other 27, 11 (41%) were alive at 3 months and 5 (19%) at 1 year. Ten of the 27 patients had cardiac tamponade, of whom 5 (50%) were alive at 3 months and 3 (30%) at 1 year. Conclusions HIV-associated pericardial effusion is the most common type of pericardial effusion in our inner city hospital. Causes are diverse. The development of pericardial effusion predicts a poor prognosis in HIV infection. (Am Heart J 1999;137:516-21.)