Background and objective To report the outcomes of topical difluprednate 0.05% use in the closure of full-thickness macular holes. Patients and methods Retrospective chart review of 4 patients with full-thickness macular holes who received difluprednate drops 4 times daily for a minimum of 12 weeks. Main outcome measures were macular hole status assessed with optical coherence tomography, visual acuity, intraocular pressure, and complications of treatment. Results All patients had macular hole closure within 12 weeks of difluprednate exposure. Mean time to macular hole closure was 5 weeks (range, 2-12 weeks). Visual acuity improved with macular hole closure. Average baseline visual acuity was 20/42. Average visual acuity after macular hole closure was 20/26 (P = 0.14). Two patients experienced increased intraocular pressure with topical steroid use. Conclusion Exposure to difluprednate in this cohort of patients with full-thickness macular holes was associated with reduced macular edema, macular hole closure, and visual improvement.