Chronic graft-versus-host disease (cGVHD) is a leading cause of late morbidity and mortality after allogenic hematopoietic stem cell transplantation. Corticosteroid-based therapies are a mainstay of its initial treatment but there is no consensus in how to treat steroid-refractory cGVHD. Ibrutinib is a Bruton tyrosine kinase and IL-2-inducible kinase inhibitor thought to affect pathways driving cGVHD, and it was approved for the treatment of refractory cGVHD by the Food and Drug Administration (FDA) in August 2017 after a landmark phase 1b/2 study. It was the first medication approved for this indication, but how to best treat refractory cGVHD remains an open question, and there has been limited literature on ibrutinib after the FDA approval. This study sought to characterize the utilization and outcomes associated with ibrutinib use in cGVHD via a retrospective single-center study. Fifty-three patients were identified as having been treated with ibrutinib for cGVHD following FDA approval between September 1, 2017, and December 31, 2020, using an institutional data repository. Their records were reviewed for demographics, cGVHD characteristics, and outcomes. For the entire cohort, two-year overall survival was 76% (95% confidence interval [CI], 60% to 86%), with a median follow-up among survivors of 26 months (range, 1.3 to 39.5 months). However, the 2-year failure-free survival (FFS) after initiation of ibrutinib was 9% (95% CI, 2.6% to 20%), and the median FFS was 4.5 months (95% CI, 2.8 to 7.1 months). Events of FFS included treatment change due to lack of response or toxicity, malignant relapse, or non-treatment related mortality. At the time of this report, 11 patients (21%) remained on ibrutinib. At the time of the FFS event or last follow-up, 6 patients (12%) had a complete or partial response, 34 (64%) had stable disease, and 13 (25%) had progressive disease. Ibrutinib use was associated with no reduction in corticosteroid dose between ibrutinib initiation and FFS event or last follow-up (mean difference, 0.00; P = .98). The most frequently used noncorticosteroid cGVHD therapy after ibrutinib was ruxolitinib (n = 14; 33%). The most common adverse events associated with treatment discontinuation were infection (lung, skin, enterocolitis; n = 6), bleeding and bruising (hematoma, epistaxis, gastrointestinal bleed; n = 5), and muscle aches (n = 2). In a real-world setting, ibrutinib is associated with a modest response rate and FFS and its use in a narrower, more targeted patient population may be indicated.