According to the Environmental Protection Administration of Toxic Chemical Database, the production quantity of VCM (Vinly Chloride Monomer) in Taiwan was 2 million tons. VCM exposure has been associated with toxicity of the liver and was classified as a group 1 carcinogen by IARC (1987). Due to the extremely volatile property, the major exposure route is inhalation. The main urinary metabolites is thiodiglycolic acid (TDGA). Urinary TDGA can be detected by GS/MS method, but the higher detection limit (>1 mg/L) was the limitation for low exposure workers in VCM plants. In order to assess the relationship of low exposure level of VCM and health risk, development of a precise and accurate analytical method for measurement of urinary TDGA is needed. The high performance liquid chromatography electro-spray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was used as analytical instrument. The method detection limit (MDL) of developed method is 1.34 ng/mL. Forty workers in two VCM plants were recruited as subjects to measure urinary TDGA in pre- and postshift urine sample for each subject. For biomarker validation, the advanced analysis was complied to compare the measures of urinary TDGA within the thirty subjects without histories of liver or kidney diseases, taking daily vitamin supplements, and standard working hours. Study results showed that the post-shift urinary TDGA levels were significantly higher than those of pre-shift. The results showed that the developed analytical method in this study could be used for the low level VCM exposure assessment.