The objective of this study is to investigate immunogenicity and safety of the yellow fever vaccine (YFV) in HIV-infected (HIV+) patients with high CD4 T-cell counts. In this prospective, comparative study of YFV-naive adults: 40 HIV+ under antiretroviral therapy (ART) with CD4 T-cell count above 350 cells/μl and plasma HIV-RNA less than 50 copies/ml for at least 6 months and 31 HIV-negative (HIV-) received one injection of the YF-17D strain vaccine. Serologic response was assessed by using a plaque reduction neutralizing test and YFV-specific T cells by using an INFγ-Elispot assay. YFV was well tolerated in both groups. Most participants had asymptomatic YFV viremia at day (D) 7 after vaccination (77% of HIV- and 82% of HIV+, P = 0.58), with higher plasma level of YFV RNA in HIV+ than in HIV- (median 2.46 log10 copies/ml (range: 1.15-4.16) and 1.91 log10 copies/ml (1.15-3.19), respectively, P = 0.011). A significant but transient decrease in CD4 cell counts was seen at D7 in both groups, more pronounced in HIV- than in HIV+ patients (-261.5 versus -111.5 cells/μl, respectively, P = 0.0003), but no HIV breakthrough was observed in plasma. All participants developed protective neutralizing antibody levels from D28 and up to 1 year after injection. At D91, fewer HIV+ than HIV- participants exhibited YFV T-cell response (20 versus 54%, respectively, P = 0.037). At 1 year, YFV was immunogenic and well tolerated in HIV-infected adults under ART with CD4 T-cell counts above 350 cells/μl. However, a lower immunity of YFV T cells in HIV-infected patients was observed as compared with HIV- participants. NCT01426243.