We compared the clinical characteristics and outcomes of 100 patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL; HIV-NHL) treated in the highly active antiretroviral therapy era with those of 82 HIV-negative patients with aggressive NHL. The 3-year overall survival (OS) was 37% among patients with HIV-NHL and 74% among HIV-negative patients with NHL (P<.0001). However, the response-adjusted OS was similar in the 2 groups (hazard ratio, 1.4 for HIV-infected patients vs. 1 for HIV-negative patients; P=.24). Therefore, the achievement of complete remission should be the main goal in the treatment of patients with HIV-NHL.