To demonstrate the efficacy of the anti-interleukin-6 receptor monoclonal antibody tocilizumab in patients with moderate-to-severe corticosteroid-resistant Graves orbitopathy (GO). Double-masked randomized clinical trial. Setting and Participants: Thirty-two adults with moderate-to-severe corticosteroid-resistant GO from 10 medical centers in Spain were randomized (1:1). Intervention: Randomization to either 8 mg/kg body weight tocilizumab or placebo administered intravenously at weeks 0, 4, 8, and 12, and follow-up for an additional 28 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients with a change from baseline to week 16 of at least 2 in the clinical activity score (CAS). The primary outcome was met by 93.3% (95% confidence interval CI 70.1%-98.8%) of the patients receiving tocilizumab and 58.8% (36%-78.3%) receiving placebo (P = .04; odds ratio, 9.8 CI 1.3-73.2). A significant difference was also observed in the proportion of patients achieving a CAS < 3 (86.7% CI 62.1%-96.2% vs 35.2% CI 17.3%-58.7%, P = .005; OR 11.9 CI 2.1-63.1) at week 16. Additionally, a larger proportion of patients with improvement in the European Group on GO–proposed composite ophthalmic score at week 16 (73.3% CI 48%-89.1% vs 29.4% CI 13.2%-53.1%; P = .03), and exophthalmos size change from baseline to week 16 (-1.5 -2.0 to 0.5 mm vs 0.0 -1.0 to 0.5 mm; P = .01) were seen with tocilizumab. One patient experienced a moderate increase in transaminases at week 8; another had an acute pyelonephritis at week 32 in the tocilizumab-treated group. Tocilizumab offers a meaningful improvement in activity and severity in corticosteroid-resistant GO. This trial justifies further studies to characterize the role of tocilizumab in GO.