Purpose To report the results of interferon (IFN) alpha-2a treatment in patients with cystoid macular edema (CME) secondary to acute retinal necrosis (ARN). Methods We reviewed the records of seven patients (eight eyes) who received IFN alpha-2a for post-ARN CME. The initial dose of IFN alpha-2a was 3 MIU/day and it could be tapered down to 3 MIU twice a week. Efficacy was assessed by central macular thickness (CMT) on spectral-domain optical coherence tomography and visual acuity. Results Age range of seven patients (four men, three women) was 36-74 years. Mean CMT decreased from 477.9 +/- 167.5 mu m to 367.3 +/- 120.5 mu m at first week, and vision improved up to five lines in five eyes. CME relapsed after cessation of IFN alpha-2a in all and improved following reinstitution of treatment. Treatment was discontinued in one patient because of depression. Three patients electively discontinued treatment due to poor tolerability or lack of functional improvement. Conclusion IFN alpha-2a is an effective therapeutic option for post-ARN CME, though side effects such as fatigue, elevated liver enzymes, neutropenia, and depression may limit tolerability. Lower initial doses may be a better tolerated.