Chlorpyrifos is the most common organophosphate compound registered for agricultural use in Vietnam. The aim of this study was to evaluate chlorpyrifos exposure to rice farmers in Vietnam, using a probabilistic approach. Urine samples on a 24-h basis were collected from farmers before and post application of pesticide. Samples were analysed for 3,5,6-trichloro-2-pyridinol (TCP), the major urinary metabolite of chlorpyrifos, using an enzymatic pre-treatment for extraction and HPLC-MS/MS. Absorbed daily doses (ADD) of chlorpyrifos for farmers were subsequently estimated from the urinary TCP levels. The baseline and post-application exposure levels were evaluated at the 5th, 50th, and 95th percentile representing low, medium and high-exposure groups in the population. Regression analysis was applied to examine the association between exposure level and factors. The baseline exposure level, which ranged from 0.03 to 1.98 μg/kg/day was below the chronic guidelines recommended by international and national bodies. However, the post-application exposure level, which ranged from 0.35 to 94 μg/kg/day exceeded most of the acute guidelines at the 95th percentile level. Multivariate analysis provided strong evidence for a relationship between post-application exposure level and amount of chlorpyrifos used, as well as body coverage of personal protective equipment.