ABSTRACT Purpose To report the efficacy of pegylated interferon alpha-2a (Roferon, Hoffmann-La Roche brands, Switzerland) in uveitic macular edema refractory to biologic agents. Methods Herein, we present two cases of non-infectious uveitis with cystoid macular edema (CME) who were unresponsive to immunosuppressant treatment, and whose uveitis and macular edema recurrences were prevented with subcutaneous injections of pegylated interferon α-2a. Results Two young males (27- and 30-year-old) diagnosed with non-infectious uveitis and CME were on immunosuppressive treatment. Although both received systemic steroids and biologic agents, macular edema persists. After initiation of pegylated interferon alpha-2a (Pegasys, Genentech, USA) CME regressed significantly and did not occur during their follow-ups of 14 and 12 months. Conclusion Pegylated interferon-alpha-2a can be used as an effective alternative to interferon alpha-2a in uveitic macular edema cases, resistant to other immunosuppressive agents.