OBJECTIVES: To determine the effect of antiretroviral therapy (ART) on the immunological and virological outcomes of older human immunodeficiency virus (HIV)-infected patients compared with younger HIV-infected patients. DESIGN: Matched (1:2) retrospective case-control study (1993-1999). SETTING: Duke University Infectious Diseases Clinic. PARTICIPANTS: One hundred one older patients, mean age 56.7 (range 50-79) and 202 younger patients, mean age 32.8 (range 21-39). Patients were matched on baseline CD4+ cell count and date of clinic entry. MEASUREMENTS: The virological and immunological outcomes were viral suppression (HIV ribonucleic acid (RNA) level ≤400 copies/ml) and change in CD4+ cell count. To estimate differences in antiretroviral drug exposure, the percentage of patients on ART overall and by drug class was compared. To assess antiretroviral drug exposure further, the percentage of patients having interruptions in ART was compared. RESULTS: The older and younger groups had similar baseline CD4+ cell counts (332 vs 306 cells/mm3; P = .31) and similar increases in CD4+ cell counts (+3.47 vs +4.60 cells/mm3/month; P = .37) over a mean ± standard deviation of 2.4 ± 1.7 years of follow-up. The older group had a higher percentage of patients with current plasma HIV RNA levels less than 400 (46% vs 34%; P = .05). The groups had similar rates of non-nucleoside reverse transcriptase, nucleoside reverse transcriptase, and protease inhibitor use. The older group had fewer interruptions in ART than the younger group (11% vs 26%; P = .01). CONCLUSIONS: Older HIV-infected patients responded well to ART, with a significantly greater percentage achieving a current plasma HIV RNA below detectable limits. Older patients experienced similar increases in CD4+ cell count as younger matched controls. Older patients were less likely to interrupt ART, which suggests better adherence and/or tolerance and may explain the higher rate of HIV RNA suppression.