The prospective, multicenter cohort study EuroSIDA has previously reported on predictors and outcomes of anemia in patients infected with human immunodeficiency virus. In a Cox proportional-hazards model with serial measures of CD4+ cell count, plasma viral load, and degrees of anemia fitted as time-dependent variables, the relative hazard of death increased markedly for patients with anemia versus no anemia. A clinical scoring system was developed and validated for patients receiving highly active antiretroviral therapy using the most recent laboratory measures. Mild and severe anemia were independently (P<.01) associated with clinical disease progression, with a relative hazard of disease progression of 2.2 (95% confidence interval [CI], 1.6-2.9) and 7.1 (95% CI, 2.5-20.1), respectively, compared with patients with no anemia. The mechanisms underlying why hemoglobin is such a strong prognostic marker and whether correction of anemia itself results in a better prognosis remain to be determined.