Objective: To compare the efficacy and tolerability of tacrolimus and cyclosporine therapy for noninfectious posterior segment intraocular inflammation and to evaluate their effect on peripheral blood CD4+T-cell phenotype and activation status. Method: Thirty-seven patients who required secondline immunosuppression for posterior segment intraocular inflammation were enrolled in this prospective randomized trial of tacrolimus vs cyclosporine therapy. The main outcome measures were visual acuity, binocular indirect ophthalmoscopy score, adverse effects, and quality of life. In addition, peripheral blood CD4+T-cell phenotype and activation status were evaluated by flow cytometry before treatment and at 2, 4, and 12 weeks using CD69, chemokine receptor (CCR4, CCR5, and CXCR3), and intracellular cytokine (tumor necrosis factor α, interferon-γ, and interleukin 10) expression. Results: Thirteen patients (68%) taking tacrolimus and 12 patients (67%) taking cyclosporine responded to treatment. Cyclosporine therapy was associated with a higher incidence of reported adverse effects. Mean arterial pressure and serum cholesterol level were significantly higher at 3 months in the cyclosporine group than the tacrolimus group. No significant difference was detected with regard to effect on quality of life or CD4+T-cell phenotype. Conclusion: Tacrolimus and cyclosporine were similar with regard to ef-ficacy for posterior segment intraocular inflammation, but the results suggested a more favorable safety profile for tacrolimus therapy. Objective: To compare the efficacy and tolerability of tacrolimus and cyclosporine therapy for noninfectious posterior segment intraocular inflammation and to evaluate their effect on peripheral blood CD4 + T-cell phenotype and activation status. Method: Thirty-seven patients who required secondline immunosuppression for posterior segment intraocular inflammation were enrolled in this prospective randomized trial of tacrolimus vs cyclosporine therapy. The main outcome measures were visual acuity, binocular indirect ophthalmoscopy score, adverse effects, and quality of life. In addition, peripheral blood CD4 + T-cell phenotype and activation status were evaluated by flow cytometry before treatment and at 2, 4, and 12 weeks using CD69, chemokine receptor (CCR4, CCR5, and CXCR3), and intracellular cytokine (tumor necrosis factor α, interferon-γ, and interleukin 10) expression. : Thirteen patients (68%) taking tacrolimus and 12 patients (67%) taking cyclosporine responded to treatment Mean arterial pressure and serum cholesterol level were significantly higher at 3 months in the cyclosporine group than the tacrolimus group. No significant difference was detected with regard to effect on quality of life or CD4 + T-cell phenotype. Conclusion: Tacrolimus and cyclosporine were similar with regard to ef-ficacy for posterior segment intraocular inflammation, but the results suggested a more favorable safety profile for tacrolimus therapy.