Human health risk assessments of exposures to non-carcinogenic occupational and environmental toxicants have mostly been undertaken using the Hazard Quotient (HQ) approach, which largely ignores variabilities in both exposures and associated adverse health outcomes, unlike probabilistic approaches. Chlorpyrifos is a neurotoxic insecticide that is commonly applied by farmers in Ghana with limited research on associated health risks among applicators. The objective of this study was to assess health risks associated with chlorpyrifos exposure among applicators on rice farms in Ghana, using advanced probabilistic approaches that incorporate variability in both exposure doses and adverse response doses obtained from human epidemiological studies. Urine samples obtained from the applicators were analyzed for 3,5,6-trichloro-2-pyridinol (TCP)from which Absorbed Daily Dose (ADD) and Lifetime Average Daily Dose (LADD) levels of chlorpyrifos were estimated. The scientific literature was searched to identify human epidemiological data from studies that have reported chlorpyrifos adverse effects and their corresponding exposure levels. Equivalent ADD and LADD of chlorpyrifos were estimated from the human epidemiological data to obtain chlorpyrifos Toxicant Sensitivity Distributions (TSDs). Using the applicators' chlorpyrifos dose distribution and TSDs, adverse health risks among the applicators were characterized using the probabilistic approaches, Overall Risk Probability (ORP) and Monte Carlo Simulation (MCS). The probabilities of chlorpyrifos adverse health effects occurring under the chronic exposure scenarios ranged from 1 to 8%, while those for acute exposure scenarios ranged from 31 to 34%. This study indicates that while the risks of chronic adverse health effects from chlorpyrifos exposure among the applicators were low, acute health risks were high.