Canine osteosarcoma is the most common bone cancer, and an important cause of mortality and morbidity, in large purebred dogs. Previously we constructed two multivariable models to predict a dog's 5-month or 1-year mortality risk after surgical treatment for osteosarcoma. According to the 5-month model, dogs with a relatively low risk of 5-month mortality benefited most from additional chemotherapy treatment. In the present study, we externally validated these results using an independent cohort study of 794 dogs. External performance of our prediction models showed some disagreement between observed and predicted risk, mean difference: -0.11 (95% confidence interval [95% CI]-0.29; 0.08) for 5-month risk and 0.25 (95%CI 0.10; 0.40) for 1-year mortality risk. After updating the intercept, agreement improved: -0.0004 (95%CI-0.16; 0.16) and -0.002 (95%CI-0.15; 0.15). The chemotherapy by predicted mortality risk interaction (P-value = 0.01) showed that the chemotherapy compared to no chemotherapy effectiveness was modified by 5-month mortality risk: dogs with a relatively lower risk of mortality benefited most from additional chemotherapy. Chemotherapy effectiveness on 1-year mortality was not significantly modified by predicted risk (P-value = 0.28). In conclusion, this external validation study confirmed that our multivariable risk prediction models can predict a patient's mortality risk and that dogs with a relatively lower risk of 5-month mortality seem to benefit most from chemotherapy.