Objective To evaluate the effectiveness of PTD regimen (pamidronate disodium + thalidomide + dexamethasone) and TD regimen (thalidomide + dexamethasone) in the treatment of multiple myeloma. Methods The patients meeting the inclusion criteria were randomly treated with PTD and TD regimens from January 2004 to December 2008. The effectiveness and safety of the two groups were observed after 8 weeks and the statistical analyses were performed using SPSS 13.0 software. Results A total of 25 patients were included, of which 13 were treated with PTD regimen and the other 12 were treated with TD regimen. The results showed overall response rates were 84.6% and 83.3% in the PTD and TD groups, respectively, with no significant difference (Pgt;0.05). The complete response rate (5/13 vs. 1/12) and early response rate (within 2 weeks, 4/13 vs. 1/12) for bone pain in the PTD group were better than those of TD group (Plt;0.05). Conclusion Compared with TD regimen, PTD regimen has more dramatic and faster effects on bone pain relief for multiple myeloma, but for overall response rate, further larger sample size randomized controlled trials are needed.