AIM:To evaluate the efficacy of multilayer amniotic membrane transplantation combined with antivirus and glucocorticosteroid drug to treat necrotizing herpes simplex stromal keratitis. METHODS: Eighteen patients (18 eyes) of necrotizing herpes simplex stromal keratitis were referred to the central hospital of Enshi Autonomous Prefecture between October 2002 and October 2009. Corneal inflammation persisted and corneal ulcer progressed despite topical and systemic antiviral treatment for over 1 week. Multilayer fresh amniotic transplantation was performed, and combined with antivirus and glucocorticosteroid drug after operation. RESULTS: Corneal ulcer healed after operation. Corneal transparence was achieved in 8 cases, partial corneal leucoma or macula in 10 cases. 1 of these patients, whose ulcer progressed to hole, adherent leucoma was formed, and corneal transplant was performed in 1 year. CONCLUSION:Multilayer fresh amniotic transplantation combined with antivirus and glucocorticosteroid treatment is an efficient method to treat necrotizing stromal keratitis. The method can recover some visual acuity, or keep the integrity of cornea for corneal transplantation.