The first trial of the efficacy of a human immunodeficiency virus (HIV)-1 vaccine was conducted in North America and The Netherlands between 1998 and 2003. This multicenter, randomized, placebo-controlled trial of a recombinant glycoprotein 120 vaccine included 5403 initially HIV-negative volunteers who were monitored for 3 years. The 368 subjects who acquired HIV-1 infection were monitored for 2 years by use of the following postinfection end points: plasma HIV-1 RNA level (viral load), CD4+ lymphocyte count, initiation of antiretroviral therapy (ART), and HIV-1-related clinical outcomes. This article reports the study results that pertain to the effect of vaccination on the postinfection end points. The time until initiation of ART and the time until virologic failure or initiation of ART were similar in the vaccine arm and the placebo arm. The pre-ART viral load and CD4+ lymphocyte count trajectories were also comparable between the groups. Evidently, the vaccine did not affect HIV-1 disease progression.