Pneumonectomy is necessary when disease either extends into multiple lung lobes on the same side or invades the primary bronchus resulting in close proximity to the hilus, limiting the disease-free margin obtained via simple lung lobectomy. In this study, right and left pneumonectomy was performed from both a median sternotomy and lateral thoracotomy surgical approach in nine canine cadavers. Surgical techniques using a thoracoabdominal stapler versus a hand-tie method for individual anatomic ligation from the lateral thoracotomy approach were further compared. Distance from the carina and proximal-most aspect of the lung parenchyma were measured in all approaches and techniques. Right and left lateral thoracotomy approaches consistently allowed transection or ligation closer to the carina and farther from the pulmonary parenchyma than via median sternotomy. From a lateral thoracotomy, greater tissue distance from pulmonary parenchyma and closer proximity to the carina was achieved with individual anatomical ligation via hand-ties compared to the stapler technique. When performing pneumonectomy, lateral thoracotomy allows for greater tissue dissection and possibly will allow for wider surgical margins at the hilus than a median sternotomy approach. Additional dissection using hand-tie ligation over thoracoabdominal stapling devices may allow greater margins from a lateral thoracotomy.