Objectives The purpose of this study was to evaluate the safety and efficacy of cryoablation in a closed chest canine epicardial ablation model. Background Limitations of radiofrequency energy in the epicardial space warrants investigation of alternative energy sources. Methods A linear-tip catheter with a 3-cm freezing element and a 6-mm-tip catheter were used to create epicardial atrial and ventricular cryolesions. Epicardial coronary arteries were targeted to evaluate the effects of cryoablation on epicardial vessels. Cryoablation was performed at −90°C for 4 minutes per lesion. Pathologic examination of the hearts was performed. Lesions were stained with tetrazolium chloride, analyzed grossly, and examined histologically. Results Ten of 11 linear catheter atrial lesions were transmural (average depth 1.5 ± 1.3 mm). Only three of 13 6-mm-tip atrial lesions were transmural (average depth 1.1 ± 1.2 mm). Ventricular lesions were continuous and not transmural (average depth of lesion for the linear and 6-mm-tip catheters: 2.7 ± 1.3 mm and 1.6 ± 0.7 mm, respectively). Angiographic stenosis (20–100%) during freezing was detected in 9 of 28 lesions, with TIMI III flow present in all vessels 5 minutes following thaw. Neointimal proliferation was present in 13 vessels, with no evidence of damage in vessels with internal diameters greater than 0.7 mm. Occlusive injury was identified in one small branch vessel. Conclusions Creation of transmural lesions was possible in the atria but not in the ventricles. Cryothermal ablation can cause neointimal proliferation, with the probability that damage will be directly proportional to lesion depth and inversely proportional to vessel diameter.