PURPOSE: To describe characteristics of patients with severe limbal stem cell deficiency associated with contact lens (CL) wear. DESIGN: Retrospective case series. METHODS: Database search of patients with severe limbal stem cell deficiency related to CL wear was conducted. The charts of 12 patients (18 eyes) were reviewed. Outcome measures included patient demographics, CL type, duration of wear, indications for wear, symptoms, location and laterality of limbal stem cell deficiency, coexisting ocular disease, and treatment. RESULTS: Mean patient age at presentation was 42 years (range, 19 to 58 years), and 8 patients (67%) were female. Mean duration of CL wear was 14.1 years (range, 1 to 20 years), 6 patients (50%) had bilateral disease, and all wore soft CLs for refractive error correction. Vision was decreased to a mean of 20/78 (range, 20/30 to 20/250) in all eyes. Fifteen eyes (83%) had photophobia, pain, or both. Findings leading to the diagnosis included whorl-like epitheliopathy, corneal conjunctivalization, and late fluorescein staining of the involved epithelium for at least 6 clock hours. On average, 10 clock hours (range, 6 to 12 clock hours) were involved, and 11 eyes (61%) had total ocular involvement. Conservative treatments failed in all eyes. Fourteen eyes (78%) underwent limbal stem cell transplantation with systemic immunosuppression. CONCLUSIONS: Severe limbal stem cell deficiency related to CL wear is a clinical diagnosis that an ophthalmologist should recognize. Female patients, soft CLs, and extended duration of wear time are associated with this condition. Conservative measures may not reverse the disease, and limbal stem cell transplantation with systemic immunosuppression is a surgical option for these young and healthy patients. (Am J Ophthalmol 2013;155: 544-549. (C) 2013 by Elsevier Inc. All rights reserved.)