Ninety-five dogs with either a presumptive (n = 24) or biopsy confirmed diagnosis (n = 71) of osteosarcoma received palliative radiotherapy using 60Co photons. Parallel opposed beams were used with each dog receiving either 10 Gy on days 0, 7 and 21 (n = 58) or 8 Gy on days 0 and 7 (n = 37). The 8 Gy fractionation scheme was given with the intent of retreating upon relapse from pain relief. Only 9 of 37 (24%) dogs in the 8 Gy group returned for retreatment. Forty-seven of the 95 dogs (49%) received concurrent or sequential chemotherapy. Seventy of the 95 dogs (74%) experienced pain relief following treatment. In dogs experiencing pain relief the median duration of response was 73 days. Numerous clinical variables were evaluated as predictors of response. The only variable significantly related to achieving a response was the use of chemotherapy. The following variables were significantly related to the duration of response: extent of bone lysis, chemotherapy use, length of bone involved and tumor site (humerus). In a multivariate analysis (n = 73 dogs), after adjusting for chemotherapy use, extent of bone involvement (p = 0.01) and tumor site (p = 0.02) retained statistical significance, while degree of bone lysis did not (p = 0.11). No difference in response incidence or duration was found between 3 fractions of 10 Gy vs. 2 fractions of 8 Gy. Administration of a low initial dose with the intent of retreatment was not a successful strategy.