Synthesis of the medicinal intermediate (R)-(-)-3-chloro-2-hydroxypropyl tosylate was carried out by the reaction of (R)-(-)-3-chloro-1,2-propanediol and p-toluenesulfonyl chloride in this paper. The influences of the reaction temperature, reaction time, type and dosage of solvent, type and dosage of catalyst, and (R)-(-)-3-chloro-1,2-propanediol/p-toluenesulfonyl chloride ratio on the selectivity of esterification and yield of product were investigated. The suitable synthesis conditions were obtained by optimization with orthogonal experiments: reaction temperature 0°C, reaction time 6h, the molar ratio of p-toluenesulfonyl chloride to (R)-(-)-3-chloro-1,2-propanediol 1.2:1, the molar ratio of catalyst NaOH to (R)-(-)-3-chloro-1,2-propanediol 1.2:1. Ethyl acetate was used as solvent, and the concentration of (R)-(-)-3-chloro-1,2-propanediol was 125g/L. The yield of (R)-(-)-3-chloro-2-hydroxypropyl tosylate was over 85%.