The effect of the levonorgestrel-releasing intrauterine device (LNG-IUD) on genital HIV-1 RNA shedding and inflammation among 25 HIV-infected women was evaluated. Blood, endocervical, and cervicovaginal lavage samples were collected from HIV-infected women not taking antiretrovirals before LNG-IUD insertion and 1 month, 3 month, and 6 months thereafter. HIV-1 RNA was quantitated by real-time reverse transcriptase-polymerase chain reaction. Inflammatory markers were measured by enzyme immunoassay. Genital HIV-1 RNA shedding and inflammatory markers did not differ between LNG-IUD placement and month 6, with the exception of interleukin 1β that increased (0.42 log10; 95% confidence interval: 0.10 to 0.75). The LNG-IUD did not increase genital HIV-1 RNA shedding after 6 months of use.