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Digital clubbing is characterized by bulbous enlargement of the distal phalanges due to an increase in soft tissue. It has been associated with a variety of conditions including cyanotic heart disease, neoplasms and infections of the lungs, bronchiectasis, liver cirrhosis, and inflammatory bowel disease. We conducted an observational study at an urban Veterans Affairs Medical Center outpatient HIV clinic to confirm our clinical impression that clubbing is common in HIV-infected patients and to identify factors that might be associated with it. Clinical, laboratory, and physical examination data including measurement of the circumference of the nail bed and distal phalanx of each finger were obtained on 78 HIV-infected patients seen for their routine care over a 3-month period. A digital index (DI), the ratio of the nail bed:distal phalanx circumference was determined for each patient. Clubbing was found in 28 patients (36%). Clubbed patients did not differ from nonclubbed patients with respect to most patient characteristics; CD4 cell counts and quantitative HIV RNA were similar in both groups. Clubbed patients had a significantly higher DI than controls (1.03 versus 0.96, p < 0.001), were younger (45 versus 49 years, p = 0.04), and had longer duration of HIV disease (48 versus, 42 months, p = 0.03). HIV infection should be considered in the differential diagnosis of acquired digital clubbing.