Purpose: To find out whether intravitreally administered bevacizumab and ranibizumab affect the contralateral, untreated, eyes of patients with bilateral diabetic macular edema (DME). Methods: A retrospective review of patients with bilateral DME, who were treated with intravitreal bevacizumab or ranibizumab, was performed. All enrolled patients received intravitreal 1.25 mg bevacizumab or 0.5 mg ranibizumab in the eye with more severe macular edema. As outcome measures, best-corrected visual acuity (BCVA) was assessed with the Early Treatment Diabetic Retinopathy Study chart and central foveal thickness (CFT) measurement was obtained using optical coherence tomography-3 before and at 2 and 4 weeks after injections. Results: The study included 55 eyes of 55 patients who received bevacizumab (group 1) and 32 eyes of 32 patients who received ranibizumab (group 2). The mean age of the 55 patients [35 female (63.6%), 20 male (36.4%)] in group 1 was 54.31±12.67 years, and the mean age of the 32 patients [20 female (62.5%), 12 male (37.5%)] in group 2 was 56.01±13.29 years. The median BCVA in the uninjected eye showed no statistically significant change at any visit after either bevacizumab or ranibizumab injection (P=0.302, P=0.582, respectively). In group 1, the median CFT in the uninjected eye was 417 μm at baseline; this was reduced to 401 μm at 2 weeks and 372 μm at 4 weeks. The change in CFT was found to be statistically significant (P=0.009). No statistically significant change was found in the median CFT of uninjected eyes of patients treated with ranibizumab (399, 403, and 407 μm before and at 2 and 4 weeks after treatment, respectively). Conclusions: Compared with ranibizumab, intravitreal administration of bevacizumab resulted in a greater decrease in macular thickness in the untreated eye, in patients with bilateral DME. © Mary Ann Liebert, Inc. 2013.