•Uncontrolled, chronic anterior uveitis leads to ocular morbidity in children.•Failed treatment with methotrexate and adalimumab and/or infliximab is not uncommon.•Alternative biologic agents include golimumab, tocilizumab, and abatacept.•Nine patients with resistant disease were successfully treated with alternative biologic agents. A significant number of children with noninfectious, chronic anterior uveitis (CAU) fail to respond to conventional therapy; however, successful alternative biologic treatments (ABT) have not been well described. This study aims to review the clinical and treatment characteristics of children with CAU who require ABT. Retrospective, nonrandomized clinical study. Setting: Tertiary center. Study Population: Children with noninfectious CAU. Observation Procedures: Clinical characteristics, uveitis course, complications, and treatment were compared among patients treated with methotrexate (MTX) monotherapy, conventional TNFα inhibitors (cTNFi), and ABT for >3 months. Main Outcome Measure: Success of ABT (abatacept, tocilizumab, and/or golimumab) in children failing conventional treatment. Of the 52 children with CAU, 75% had juvenile idiopathic arthritis. CAU was controlled in 15 children receiving MTX monotherapy, 28 receiving cTNFi, and 9 receiving ABT (n = 1, abatacept; n = 3, tocilizumab; n = 5, golimumab). Patients in the ABT group had a greater number of total ocular complications per person before ABT than those in the control groups (3.4 vs 0.7 MTX, P < .001, and 1.5 cTNFi, P < .001, respectively). In all 9 children on ABT, treatment led to control of CAU and topical glucocorticoids tapered to ≤2 drops/d with no new ocular complications. In this study, alternative biologics (abatacept, golimumab, and tocilizumab) were useful for treating CAU in children who fail MTX and cTNFi therapy. Patients who were controlled on ABT had more disease activity, ocular complications, and anti-cTNFi neutralizing antibodies (before ABT) than those managed with conventional therapy. Larger studies are required to confirm these findings.