Invasive pneumococcal diseases remain frequent and severe in HIV-infected subjects. To identify opportunities for prevention, we assessed risk factors of invasive pneumococcal diseases (IPD) in HIV-infected patients over a 10-year period in France. We performed a retrospective case-control study in a reference centre of HIV management in Paris. All HIV-infected patients having suffered from IPD between 2000 and 2011 were included. Control subjects were HIV-infected with no history of IPD or pneumonia, matched by date of diagnosis of HIV with controls. Two controls were randomly selected for each subject. In all, 42 HIV-infected patients presented 44 IPD episodes during the study period and were compared to 84 controls. In the multivariate analysis, patients with IPD were more likely than controls to have a Charlson Comorbidity Index ≥2 (adjusted OR = 7.07, 95% CI 1.99–25.1, p = 0.003), CD4-cell count <200/cells/µL (aOR = 6.93, 95% CI 1.80–26.7, p = 0.005), HIV-RNA viral load >400 copies/mL (aOR = 5.56, 95% CI 1.58–19.5, p = 0.007) and a non-European origin (aOR = 4.26, 95% CI 1.02–17.9, p = 0.047). HIV-infected patients with a higher burden of comorbidities, uncontrolled HIV replication, low CD4-cell counts and/or of non-European origin are at higher risk of developing IPD. Better screening for and management of HIV infection is necessary to reduce the risk of IPD.