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To describe the cases of anal cancer that appeared in the French Hospital Database on HIV between 1992 and 2004 and to study risk factors of anal cancer.We examined the incidence rates of anal cancer between 1992 and 2004 and the risk associated among 86 322 HIV-infected patients included in the French Hospital Database on HIV.We identified 132 cases of anal cancer, including 124 cases in men (94%), of whom 75% had sex with men. Median age at diagnosis was 42.8 years (interquartile range: 36.9–49.4). At diagnosis, 103 patients (78%) were receiving combination antiretroviral therapy for a median of 37.1 months (interquartile range: 4.5–59.8). Median survival after anal cancer diagnosis was 5 years. The respective overall incidence rates of anal cancer per 100 000 person-years between 1992 and March 1996, April 1996 to 1998 and between 1999 and 2004 were 11 (95% confidence interval, 4–17), 18 (95% confidence interval, 10–27) and 40 (95% confidence interval, 32–47). The risk of anal cancer was higher among men who have sex with men. After adjustment for age at inclusion in the study, as well as gender, the HIV transmission group, the nadir CD4 cell count and AIDS status, the incidence was higher in the years 1999–2004 than in between 1992 to March 1996 (hazard ratio, 2.5; 95% confidence interval, 1.2–5.3), with no change in the years 1999–2004.The incidence of anal cancer has increased among HIV-infected patients in France since 1996. Although an ascertainment bias cannot be excluded, data indicate that combination antiretroviral therapy does not prevent anal cancer in these patients. This supports the urgent need for developing anal cancer screening programs for HIV-infected men who have sex with men.