Abstract: OBJECTIVE To optimize the synthesis process of cisatracurium besylate. METHODS Using 3,4-dimethoxyphenethylamine and (3,4-dimethoxyphenyl) acetic acid as starting material, tetrshydropapaverine was prepared by acylation, dehydration cyclization and reduction reaction. The semi-quantitative method was used to obtain R-tetrshydropapaverine with (+)-Di-1,4-toluoyl-D-tartaric acid as resolving agent. Then cisatracurium besylate was synthesized by michael addition reaction and methylation reaction. RESULTS The structure of the target product was confirmed by MS, ¹H-NMR, and ¹³C-NMR. The HPLC indicated that the purity of product was 99.18%, and the total yield was 24.79%. CONCLUSION The optimized process have the characteristics such as short reaction time, simple operation and highly yield, which provide significant information and basis for industrial production.