To examine safety and efficacy of bandage soft contact lenses (BSCLs) for ocular chronic graft-versus host disease (GVHD), we conducted a phase II clinical trial. Extended-wear BSCLs were applied under daily topical antibiotics prophylaxis. Patients completed standardized symptom questionnaires at enrollment and at 2 weeks, 4 weeks and 3 months afterwards. Ophthalmologic assessment was performed at enrollment, at 2 weeks and afterwards as medically needed. Assessments at follow-up were compared with baseline by paired t-test. Nineteen patients with ocular GVHD who remained symptomatic despite conventional treatments were studied. The mean Lee eye subscale score was 75.4 at enrollment, and improved significantly to 63.2 at 2 weeks (p=0.01), to 61.8 at 4 weeks (p=0.005) and to 56.3 at 3 months (p=0.02). The ocular surface disease index score and 11-point eye symptom ratings also improved significantly. According to the Lee eye subscale, clinically meaningful improvement was observed in 9 patients (47%) at 2 weeks, in 11 (58%) at 4 weeks and in 9 (47%) at 3 months. Visual acuity improved significantly at 2 weeks compared with enrollment values. Based on slit lamp exam at 2 weeks, punctate epithelial erosions improved in 58% of the patients, showed stability in 16% and worsened in 5%. No corneal ulceration or ocular infection occurred. BSCLs are a widely available, safe and effective treatment option that improves manifestations of ocular graft-versus host disease in approximately 50% of patients. This study was registered at www.clinicaltrials.gov as NCT01616056.