OBJECTIVE Sustained-release ganciclovir implants are effective in delaying progression of newly diagnosed cytomegalovirus (CMV) retinitis. An uncontrolled case series was assembled to evaluate the efficacy of the intravitreal ganciclovir implant for patients with sight-threatening CMV retinitis who had previously failed to respond to intravenous ganciclovir and/or foscarnet. METHODS Between August 1993 and March 1995, 72 eyes of 55 patients received intravitreal ganciclovir implants. Patients were examined monthly after implant surgery. RESULTS A total of 56 eyes (77.8%) were available for evaluation after implant surgery. At the 1-month postoperative visit, 48 eyes (85.7%) of 38 patients had no progression. Implants failed to control progression at the 1-month visit in eight eyes (14.3%) of six patients receiving primary implants. A total of 32 eyes (57.1%) of 29 patients did not experience three-line loss of visual acuity through the follow-up period. The median time to three-line loss was 190 days from implantation. Four eyes (7.1%) developed visual acuity of 20/200 or worse by the 1-month follow up. The median time from implantation to development of visual acuity of 20/200 or less was 224 days. The median survival time was 376 days from study entry. The most common postoperative complication was retinal detachment, which was observed in 12 eyes receiving implants. Additional self-limiting complications included significant vitreous hemorrhage (three eyes) and hypotony maculopathy (two eyes). CONCLUSIONS Ganciclovir implants were effective in delaying visual loss in a significant proportion of patients who failed ganciclovir or foscarnet therapy. A number of these patients, however, experienced visual loss. Although the implants can be effective as therapy for relapsed CMV retinitis, the efficacy does not appear to match that noted in initial CMV retinitis therapy.