Abstract Purpose To determine the association between anticytomegalovirus (CMV) maintenance therapy after immune recovery and immune recovery uveitis in acquired immunodeficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART). Design Observational cohort study. Methods Data were obtained on AIDS patients with CMV retinitis followed up at the AIDS Ocular Research Unit of University of California San Diego from November 1995 to October 1999. Immune recovery was defined as CD4 count greater than 50 cells/μl for more than 3 months. Patients with immune recovery uveitis presented with vitritis, cystoid macular edema, or epiretinal membrane. Statistical analyses were conducted to determine the risk of continued use of anti-CMV therapy after immune recovery and the relationship of developing immune recovery uveitis with the type of anti-CMV therapy. Results Forty-three patients (64 eyes) had healed CMV retinitis and had achieved immune recovery. Thirty-one patients (48 eyes) received anti-CMV therapy after immune recovery, and 20 patients (29 eyes) developed immune recovery uveitis. Per-eye analyses revealed a 3.8-fold increase in the odds of developing immune recovery uveitis with anti-CMV therapy compared with no treatment ( P = .02). If treated with cidofovir the odds were 3.3 greater than if treated with an alternative regimen ( P = .04), 4.1 greater if treated intravenously ( P = .01), and 5.2 greater than if not treated ( P = .004). If not treated with cidofovir, a nonsignificant increase in the risk (2.4) of immune recovery uveitis was found ( P = .15). Neither the potency nor the use of implants for noncidofovir treatment was related to the risk of recovery uveitis ( P > .62). Conclusions The use of cidofovir is a primary risk factor in the subsequent development of immune recovery uveitis. Ongoing treatment of healed CMV retinitis after immune recovery does not appear to protect against the development of immune recovery uveitis.