Objective In a large series of Caucasian patients with refractory uveitis due to Behçet disease (BD) treated with infliximab (IFX) we assessed: a) long-term efficacy and safety and b) IFX optimization when ocular remission was achieved. Methods Multicenter study of IFX-treated patients with BD uveitis refractory to conventional immunosuppressant agents.103 patients/185 affected eyes were treated with IFX as first biologic therapy as follows: 3-5 mg/kg i.v. at 0, 2, 6 and then every 4-8 weeks. a) The main outcome variables were analyzed at baseline, 1st week, 1st and 6th months and 1st and 2nd years of IFX therapy. b) After remission, based on a shared decision between patient and clinician, IFX optimization was performed. Efficacy, safety, and cost of IFX therapy were evaluated. Results In whole series (n=103), main outcome variables showed a rapid and maintained improvement, reaching remission in 78 patients after a mean IFX duration of 31.5 months. Serious adverse events were observed in 9 patients: infusional reactions (n=4), tuberculosis (n=1), Mycobacterium avium pneumonia (n=1), severe oral ulcers (n=1), palmoplantar psoriasis (n=1) and colon carcinoma (n=1). In the optimization subanalysis, the comparative study between optimized and nonoptimized groups showed: a) no differences in clinical characteristics at baseline; b) similar maintained improvement in most ocular outcomes; and c) lower severe adverse events, and d) lower mean IFX costs in optimized group (4,826.52 vs. 9,854.13 euros/patient/year). Conclusion IFX seems to be effective and relatively safe in Caucasian patients with refractory BD uveitis. IFX optimization is effective, safe, and cost-effective.