PURPOSE: To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. DESIGN: Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. PARTICIPANTS: Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1 year of continuous enrollment in the OLDW. METHODS: Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. MAIN OUTCOME MEASURES: Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. RESULTS: This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P < 0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P < 0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P = 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P = 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P = 0.04). CONCLUSIONS: Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.