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People with human immunodeficiency virus (HIV) infection and AIDS have an elevated risk for cancer. Highly active antiretroviral therapy (HAART), which has been widely available since 1996, has resulted in dramatic decreases in AIDS-related deaths.We evaluated cancer as a cause of death in a US registry-based cohort of 83,282 people with AIDS (1980-2006). Causes of death due to AIDS-defining cancers (ADCs) and non-ADCs (NADCs) were assessed. We evaluated mortality rates and the fraction of deaths due to cancer. Poisson regression assessed rates according to calendar year of AIDS onset.Overall mortality decreased from 302 deaths per 1000 person-years in 1980-1989, to 140 deaths per 1000 person-years in 1990-1995, and to 29 deaths per 1000 person-years in 1996-2006. ADC-related mortality decreased from 2.95 deaths per 1000 person-years in 1980-1989 to 0.65 deaths per 1000 person-years in 1996- 2006 (P<.01), but the fraction of ADC-related deaths increased from 1.05% to 2.47% in association with decreases in other AIDS-related deaths. Non-Hodgkin lymphoma was the most common cancer-related cause of death (36% of deaths during 1996-2006). Likewise, NADC-related mortality decreased from 2.21 to 0.84 deaths per 1000 person-years from the period 1980-1989 to the period 1996-2006 (P<.05), but the fraction of NADC-deaths increased to 3.16% during 1996-2006. Lung cancer was the most common NADC cause of death (21% of cancerrelated deaths in 1996-2006).Cancer-related mortality decreased in the HAART era, but because of decreasing mortality due to AIDS, cancers account for a growing fraction of deaths. Improved cancer prevention and treatment, particularly for non-Hodgkin lymphoma and lung cancer, would reduce mortality among people with AIDS.