Abstract Objective—To determine the perioperative mortality rate, causes of death, and risk factors for perioperative death in dogs undergoing splenectomy for splenic mass lesions. Design—Retrospective case series. Animals—539 dogs. Procedures—Medical records of dogs that underwent splenectomy for known splenic masses were reviewed. Perioperative mortality rate and causes of death were determined. Associations between potential prognostic factors and perioperative death were evaluated by multivariable logistic regression analysis. Results—41 of 539 (7.6%) dogs died during the perioperative period. Thrombotic and coagulopathic syndromes and uncontrolled bleeding from metastatic lesions were the most common causes of death. Of the variables selected for multivariable analysis, platelet count at admission, whether PCV at admission was < 30%, and development of ventricular arrhythmias during surgery were significantly associated with outcome. For each decrease in platelet count of 10,000 platelets/μL, odds of death increased by approximately 6%. For dogs with PCV < 30%, odds of death were approximately twice those for dogs with PCV ≥ 30%, and for dogs that developed intraoperative arrhythmias, odds of death were approximately twice those for dogs that did not. Conclusions and Clinical Relevance—Marked preoperative thrombocytopenia or anemia and development of intraoperative ventricular arrhythmias were identified as risk factors for perioperative death in dogs with splenic masses. The risk of death may be limited by efforts to prevent thrombotic and coagulopathic syndromes and to control all sources of intra-abdominal hemorrhage.