Purpose: Treatment of nontraumatic corneal perforation is a difficult task. The aim of our study was to retrospectively analyze predisposing conditions leading to perforation, surgical treatments, and visual outcomes. Methods: Fifty-six patients were admitted in our department for a nontraumatic corneal perforation between 1997 and 2004. Mean patient age was 69 years (range, 16-95 years) and the mean follow-up was 20.5 months (range, 6-96 months). Results: The diseases associated with perforations were neurotrophic ulcer in 24 cases (43%), peripheral immunologic ulcer in ten cases (18%), dry eye in six cases (11%), and infectious keratitis in seven cases (13%). All patients had specific adapted medical treatment before surgery. As a first procedure, we used cyanoacrylate glue in 14 cases (50% anatomic success), multilayer amniotic membrane transplantation in 23 cases (100% anatomic success), conjunctival flap in six cases, peripheral lamellar graft in three cases (33% anatomic success), emergency penetrating keratoplasty in 13 cases (31% anatomic success), and one patient's eye had to be eviscerated. Several surgical procedures were necessary in 16 cases (28%), nine patients needing total conjunctival flap at the end. We were able to achieve tectonic stability in 91% of eyes and 32% of patients recovered useful visual acuity between 20/400 and 20/50. Conclusion: Amniotic membrane transplantation is an effective method for managing corneal perforations and usually does not need a further reconstructive procedure. Visual outcome is poor when peripheral or central keratoplasty are needed. We recommend a conjunctival flap when descemetocele or perforation recurs despite previous surgical management.