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Pathologic fracture is a complication of bone cancer with probable increased risk following radiation therapy (RT). Low-dose-rate (LDR) RT can spare late-responding normal tissues by allowing intrafraction DNA repair, which could also impact tumor response. This retrospective cohort study evaluated efficacy and fracture rate in canine patients (n = 184) with confirmed or suspected appendicular osteosarcoma that received 10 Gy × 2 palliative RT on consecutive days with LDR (cobalt-60) or standard-dose-rate (SDR, linear accelerator). The overall fracture rate was 21.7%. Patients treated with SDR (600 cGy/min, n = 46) and LDR (range 21.9-83.29 cGy/min, n = 152) did not differ in pathologic fracture rates (22.4% vs. 17.4%, respectively, p = 0.54) or median survival times (231 vs. 248.5 days, respectively, p = 0.448). Pathologic fracture rates did not differ on the basis of weight (<35, 35-50, and >50 kg) or location (24% forelegs, 18% hindlegs, p = 0.44). However, no dog (n = 7) weighing less than 20 kg developed a fracture. Radiographs prior to RT were subjectively assessed for bone integrity. Dogs with predominantly lytic lesions did not have a significantly higher pathologic fracture rate (21.2%-31.69% lytic/mixed vs. 10%-12.5% proliferative, p = 0.054), suggesting that pretreatment radiographic appearance does not reflect fracture risk. Additionally, the presence of a pretreatment cortical bone defect was not associated with eventual fracture (p = 0.7). Adjunctive chemotherapy improved survival time significantly (p = 0.01). On the basis of our data, it is reasonable to compare response rates and survival outcomes in published studies using cobalt irradiation with reports using linear accelerators.