Purpose: To compare the effect of an intravitreal injection of bevacizumab alone (IVB) or combined with triamcinolone (IVB/IVT) versus triamcinolone (IVT) in patients with diabetic macular edema (DME). Methods: In this randomized three-arm clinical trial, eligible eyes were assigned randomly to one of the three study arms: the IVB group, 2 injections of 1.25 mg of bevacizumab with 6-week intervals; the IVB/IVT group, 1.25 mg of IVB with 2 mg of IVT, and the IVT group, 2 mg of IVT. The clinical course of best-corrected visual acuity and central macular thickness by optical coherence tomography was monitored for up to 12 months after the initial injection. Results: One hundred eleven eyes of 105 patients with DME completed 12 months of follow-up. The IVB/IVT group and the IVT group showed better visual acuity and reduced central macular thickness at 6 weeks and 3 months, compared with the IVB group (p = 0.041, p = 0.02 at 6 weeks; p = 0.045, p = 0.043 at 3 months, respectively). However, no significant difference in visual acuity and central macular thickness was observed between the three groups at 12 months (p = 0.088, p = 0.132, respectively). The frequency of retreatment was lower in the IVB/IVT and IVT groups during the 12-month period (p < 0.001). No significant differences in visual acuity or central macular thickness were observed between the IVB/IVT and IVT groups during the follow-up. Conclusion: IVB/IVT and IVT showed more pronounced effects during the earlier postinjection period. However, levels of visual acuity or central macular thickness at 12 months were comparable in the three study groups. No beneficial effect of the combination injection was observed.