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Antiretroviral therapy (ART) improved the survival of people living with HIV/AIDS (PLWHA) and decreased HIV-related morbidities. This study assesses the cancer incidence of all adult PLWHA in Israel by transmission routes before and after 1996. This cohort study was based on cross-matching the National HIV/AIDS and Cancer Registries of all HIV/AIDS and cancer cases reported from 1981 to 2010 with the National civil census. PLWHA were followed-up until cancer diagnosis, death, leaving Israel, or 2010, whichever occurred first. Cancer incidence was adjusted for age, and compared with the National incidence. Of all 5,154 PLWHA followed-up for 36,296 person-years, 362 (7.0%) developed cancer (997.4 cases per 100,000 person-years). Higher hazard ratios to develop cancer were demonstrated among older PLWHA, Jewish people, and intravenous drug users. Cancer incidence among PLWHA was higher in the pre-ART period than after 1997 (1,232.0 and 846.7 cases per 100,000 person-years, respectively). The incidence of AIDS-defining cancers was higher than non-AIDS-defining malignancies, and higher in the pre-ART than the post-ART period (777.0 and 467.2 cases per 100,000 person-years, respectively), while the incidence of non-AIDS-defining cancers showed the opposite trend (376.5 and 455.0 cases per 100,000 person-years, respectively). The incidence of AIDS-defining and non-AIDS-defining cancers declined between the pre-ART and the post-ART period by 2.0 to 3.4 times. PLWHA had higher rates of malignancies than the general population. In conclusion, cancer incidence among PLWHA was associated with age, and declined after ART introduction; yet it was higher than that of the general population. PLWHA may benefit from age-related cancer screening, increased adherence to ART, and reduction of environmental oncogenes. [ABSTRACT FROM AUTHOR]