Objective To compare the efficacy of dehydrated and cryopreserved heterologous corneal grafts in the management of full‐thickness corneal defects in cats and dogs. Animals Studied Sixty‐five cats (81 eyes) and 42 dogs (51 eyes) with full‐thickness corneal defects of different origin. Materials and Methods This prospective randomized trial included 132 animal eyes (81 feline and 51 canine) with different full‐thickness corneal defects. Penetrating keratoplasty with cryopreserved and dehydrated corneal grafts was performed in 57 and 75 eyes, respectively. Follow‐up lasted for 6 months. Results Optically clear cornea with mild scarring was achieved in 40.4% of cases (23/57 eyes) after cryopreserved and in 42.7% of cases (32/75 eyes) after dehydrated corneal grafting. Moderate scarring after cryopreserved and dehydrated corneal grafting was observed in 35.1% of cases (20/57 eyes) and 37.3% of cases (28/75 eyes), respectively. Severe scarring and corneal opacities with severe vision loss after cryopreserved and dehydrated corneal grafting developed in 22.8% of cases (13/57 eyes) and 18.7% of cases (14/75 eyes), respectively. In two groups of animals combined, the affected eyes were salvaged and visual function improvement of varying degree was achieved in 78.0% of cases (103/132 eyes). Transplant rejection warranted enucleation in 1.75% of cases (1/57 eyes) and 1.3% of cases (1/75 eyes) after cryopreserved and dehydrated corneal grafting, respectively. Conclusions No statistically significant differences in clinical outcomes of penetrating keratoplasty with cryopreserved and dehydrated corneal grafts were observed. Dehydrated cornea may be considered a viable alternative to cryopreserved grafts for the management of full‐thickness corneal defects.