· Background: Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection in AIDS patients. Cidofovir has proved to be highly effective in treatment of CMV retinitis. Iritis and bulbar hypotony are known as the major complications after intravenous and intravitreal use of this antiviral drug. Cystoid macular edema (CME) after intravenous application of cidofovir has not been reported. · Methods: We analyzed retrospectively the incidence of CME after intravitreal or intravenous application of cidofovir and its correlation with CD4 cell counts of the patients. · Results: Two (22.2%) of 9 eyes in the intravenous and 3 (18.8%) of 16 eyes in the intravitreal injection group developed CME. It occurred between 3 and 48 weeks after cidofovir administration. In all eyes CMV retinitis was inactive. All patients received highly active antiretroviral treatment (HAART). CME was correlated with a rapid and sustained improvement in CD4 cell counts. · Conclusion: We interpret the occurrence of CME as an immune recovery phenomenon for the following reasons. All CMEs were seen in eyes with inactive CMV retinitis and the unaffected contralateral side never developed CME. The time range of appearance between 3 and 48 weeks after cidofovir administration makes direct toxicity of cidofovir unlikely. All patients had a sustained improvement of CD4 cell counts due to HAART. No CME was reported during the use of cidofovir before the HAART era.