BACKGROUND AND OBJECTIVES: To experimentally compare and contrast the internal sclerostomy produced using a mechanical trephine with that made by an Nd:YAG laser, and to evaluate the healing patterns, efficacy, and technical advantages of each method. MATERIALS AND METHODS: Four healthy dogs with normal eyes were used in this study. The left eye of each dog had an internal sclerostomy performed with an automated mechanical trephine. The right eye of each dog had an internal sclerostomy performed with an Nd:YAG laser. Postoperatively, the intraocular pressure of each eye was measured at regular intervals. The dogs were euthanized successively at 1, 2, 3, and 4 weeks postoperatively, and the morphology of the surgical sites was studied. RESULTS: The Nd:YAG laser was easier to manipulate and technically less demanding than the mechanical trephine. However, the Nd:YAG laser induced more prominent corneal edema and conjunctival hyperemia compared with the automated trephine. Morphology of the tissue response showed tissue necrosis and greater inflammation with the Nd:YAG laser than with the automated trephine. CONCLUSIONS: These two techniques demonstrate differences in technical demands and tissue response. Both are characterized by minimal reactive fibrosis of the episcleral and Tenon's capsule fibroblast.