Abstract： Objective A certain fraction of patients failed palliative treatment of 153 Sm-ethylenediaminetetramethy lenephosphate (153Sm-EDTMP) for painful skeletal metastases were reviewd. A comparative analysis was designed to identify the factors related to therapeutic response. Methods From a 3-year multi-center clinical trial, 51 cases were collected who did not respond to an intravenous injection of 153 Sm-EDTMP at a dosage of 0.5-1.5 mCi/kg. The therapeutic efficacy was evaluated via changes of symptoms, general condition, consumption of analgesics, sum of effect product, and Karnofsky scores. The age, sex, history of treatment, tumor type, location of bony involvement, uptake ratio and number of metastases, and doses used by the patients were compared to those of the responders. Results In 51 non-responders, 43 were male, 34 suffered from lung cancer, 41 had bone lesions in the vertebrae, 39 in the pelvis, and 24 had metastases in the lower extremities. Sex distribution, tumor type and location of the lesion differed significantly between responders and non-responders. No other factor showed differences between the two groups. Though patients of younger age, and lesions with lower uptake of radiopharmaceutical seemed to fail the treatment more easily as observed clinically, this was not confirmed by statistical analysis. Conclusion The sex of the patients, certain types of primary tumors and metastases to lower parts of the body were found to influence the patients' response to a single dose of 153 Sm-EDTMP palliation. Further exploration of a better way to determine dosage and predict response for each individual case is needed.