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We sought to project the lifetime cost of medical care for human immunodefiency virus (HIV)-infected adults using current antiretroviral therapy (ART) standards.Medical visits and hospitalizations for any reason were from the HIV Research Network, a consortium of high-volume HIV primary care sites. HIV treatment drug regimen efficacies were from clinical guidelines and published sources; data on other drugs used were not available. In a computer simulation model, we projected HIV medical care costs in 2004 U.S. dollars.From the time of entering HIV care, per person projected life expectancy is 24.2 years, discounted lifetime cost is $385,200, and undiscounted cost is $618,900 for adults who initiate ART with CD4 cell count <350/μL. Seventy-three percent of the cost is antiretroviral medications, 13% inpatient care, 9% outpatient care, and 5% other HIV-related medications and laboratory costs. For patients who initiate ART with CD4 cell count <200/μL, projected life expectancy is 22.5 years, discounted lifetime cost is $354,100 and undiscounted cost is $567,000. Results are sensitive to drug manufacturers’ discounts, ART efficacy, and use of enfuvirtide for salvage. If costs are discounted to the time of infection, the discounted lifetime cost is $303,100.Effective ART regimens have substantially improved survival and have increased the lifetime cost of HIV-related medical care in the U.S.