To describe the course of cytomegalovirus (CMV) retinitis in patients with AID S in the era of highly active antiretroviral therapy (HAART). Multicenter, prosp ective, observational study. Two hundred seventy-one patients with AIDS and CMV retinitis. Follow-up every 3 months with medical history, ophthalmologic exami nation, laboratory testing, and fundus photographs. Photographs were evaluated f or relapse of the retinitis (progression) by graders at a centralized reading ce nter. Retinitis progression (movement of the border of a CMV lesion< 750 μm ove r a < 750-μm front or occurrence of a new lesion one-quarter disc area or mor e in size). The overall rate of retinitis progression was 0.10/person-year (PY) ; among those with CD4+T-cell counts of< 50/μl, it was 0.58/PY, compared to 0 .02/PY among those with CD4+T-cell counts of < 200/μl(P < 0.0001). In the mul tivariate analysis, significant risk factors for retinitis progression included a low CD4+T-cell count, positive CMV load, longer time from AIDS diagnosis, an d low Karnofsky score. Compared with the rate of retinitis progression (～3.0/PY ) reported in the pre-HAART era, the rate of retinitis progression was reduced among patients in the HAART era, even among those with low CD4+T-cell counts, who might be expected to behave most like patients from the pre-HAART era. Howe ver, these events also occurred among patients with high CD4+T-cell counts and presumed immune recovery. Continued ophthalmologic follow-up of patients with immune recovery is recommended to detect early retinitis progression. To describe the course of cytomegalovirus (CMV) retinitis in patients with AID S in the era of highly active antiretroviral therapy (HAART). Multicenter, prosp ective, observational study. Two hundred seventy-one patients with AIDS and CMV retinitis. Follow-up every 3 months with medical history, ophthalmologic exami nation, laboratory testing, and fundus photographs. Photographs were evaluated f or relapse of the retinitis (progression) by graders at a centralized reading ce nter. Retinitis progression (movement of the border of a CMV lesion <750 μm ove ra <750-μm front or occurrence of a new lesion one-quarter disc area or mor e in size). The overall rate of retinitis progression was 0.10 / person-year (PY); among those with CD4 + T Incell counts of <50 / μl, it was 0.58 / PY, compared to 0.02% PY among those with CD4 + T-cell counts of <200 / μl Factors for retinitis progression included a low CD4 + T-cell count, positive CMV load Compared with the rate of retinitis progression (~3.0 / PY) reported in the pre-HAART era, the rate of retinitis progression was reduced among patients in the HAART era, even among those with low CD4 + T-cell counts, who might be expected to behave most like patients from the pre-HAART era. Howe ver, these events also occurred among patients with high CD4 + T-cell counts and presumed immune recovery. Continued ophthalmologic follow-up of patients with immune recovery is recommended to detect early retinitis progression.