Purpose: To assess stromal thermal damage and cut regularity induced by nonmechanical Q-switched Er:YAG laser corneal trephination for penetrating keratoplasty. Methods: Corneal trephination was performed in 80 enucleated porcine eyes by Q-switched (2.94-mum) Er:YAG laser, along with donor and recipient masks made of metal or ceramic. All combinations of 0.65- or 0.96-mm spot diameter and 45- or 50-mJ/pulse energy setting were used with each of the masks at a 5-Hz repetition rate. Corneas were processed for histologic examinations. Stromal thermal damage was quantified on PAS-stained slides, and cut regularity was assessed semiquantitatively on a scale from 0 (regular) to 3 (highly irregular). Transmission electron microscopy and scanning electron microscopy were performed on selected specimens. Results: The least thermal damage (mean SD = 6.2 +/- 0.7 pm) was found in the donor ceramic group with 50-mJ/pulse energy and 0.65-mm spot diameter, while the best regularity of the cut (1.2 +/- 0.4) was found in the donor ceramic group with 45-mJ pulse energy and 0.65-mm spot diameter. Thermal damage was less pronounced in donor than in recipient corneas (P < 0.01). Smaller spot diameter (0.65 mm) led to less thermal damage (P < 0.01) than the use of a 0.96-mm spot diameter. The differences in thermal damage between ceramic and metal masks were minimal. Conclusions: After Q-switched Er:YAG laser corneal trephination for nonmechanical penetrating keratoplasty, reproducible high cut regularity and low concomitant thermal damage were observed. This is an en couraging finding in the search for a nonmechanical trephine for penetrating keratoplasty combining high precision and low cost.