To assess the safety and to conduct a preliminary assessment of efficacy of intravitreal infliximab, an anti-tumor necrosis factor antibody, for sight-threatening relapsing uveitis in Behçet disease. Prospective, noncomparative, interventional pilot study. A single intravitreal injection of infliximab (1 mg/0.05 mL) was given to 15 patients with relapsing posterior uveitis at the onset of a unilateral attack. Best-corrected visual acuity, anterior chamber cells, vitreous haze, and posterior eye segment inflammation were assessed at baseline and at 1, 7, 14, and 30 days after treatment. Ocular or extra-ocular side effects were not observed. Baseline best-corrected visual acuity (mean logarithm of minimal angle of resolution, 0.74; range, 0.15 to 1.7) improved significantly by day 7 and continued to improve through day 30 after infliximab (mean, 0.30; P < .0001). Profound decreases in anterior chamber cells and vitreous haze (both P < .0001), as well as beneficial effects in retinal vasculitis (P = .0001) and retinitis (P = .001) were evident through day 30. Cystoid macular edema persisted in 9 of 11 eyes affected, but central macular thickness decreased from a baseline mean of 434 to 309 mm at the end of follow-up (P < .0001). Lack of systemic treatment at baseline in 4 patients or background immunosuppressive medications, which remained unchanged during follow-up, did not influence significantly these responses; additional treatment was not required. These findings suggest that intraocularly produced or acting tumor necrosis factor, or both, is crucial in Behçet disease-associated relapsing uveitis and that intravitreal infliximab should be considered when systemic administration is not feasible or contraindicated. Further studies may identify patients for whom intravitreal infliximab is preferable to systemic treatment.