BACKGROUND/AIMS To compare the effectiveness and side-effect profile of two doses of interferon alpha2b (IFNalpha2b) eye-drops (1 million international units (IU)/ml versus 3 million IU/ml) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS Retrospective case series. RESULTS Thirty-five eyes were identified over an 11-year period (1996-2007). Twenty-one eyes (19 patients) with conjunctival intraepithelial neoplasia (CIN) were treated with 1 million IU/ml of topical IFN-alpha2b; 12 eyes (nine patients) with CIN were treated with 3 million IU/ml. Two patients with squamous cell carcinoma (SCC) were treated with topical interferon, one with 1 million IU/ml and one with 3 million IU/ml. Baseline demographic information was not statistically different between the two groups. In patients with CIN, topical therapy eliminated disease in 81% of eyes in the 1 million IU/ml group versus 92%, in the 3 million IU/ml group, p=0.41. The median time to OSSN resolution was 2.8 months in the 1 million IU/ml group and 1.9 months in the 3 million IU/ml group, p=0.55. Neither eye with SCC responded to interferon therapy. Topical therapy was well tolerated. After a median follow-up of 24 months, three recurrences were seen in eyes successfully treated with topical therapy. CONCLUSION In our study, there were no significant differences between the 1 million IU/ml group and the 3 million IU/ml group for the treatment of CIN.