Background No published burden of illness or cost-effectiveness studies on cyanide (CN) poisoning exist. A health economic model has therefore been developed to determine the cost-effectiveness of hydroxocobalamin (Cyanokit) in suspected and known CN poisoning. Objectives To assess the cost-effectiveness of hydroxocobalamin versus standard treatment in known or suspected CN poisoning in Belgium. Methods Probabilities for neurological sequelae and mortality were applied based on phase III trials, literature data and the hydroxocobalamin preclinical trial. Since no cost and utility data for CN poisoning exist, costs and utilities of very comparable or related diseases derived from publicly available Belgian sources and literature were applied. Direct medical costs from the public healthcare payer's perspective were used. The time horizon was 1 year. Sensitivity analyses were performed to assess the robustness of the results. Results Base-case analyses versus standard treatment revealed cost-effective results (incremental cost-effectiveness ratio=9921€/QALY) in suspected CN poisoning and dominance (more effective and cost-saving) in known CN poisoning. It was determined that 17 lives could be saved and one sequel prevented per year on a national level using hydroxocobalamin treatment. One-way sensitivity analyses varying efficacy, costs, utilities and time horizon demonstrated the robustness of the results. The results were most sensitive to the probability of death and neurological sequelae, but remained within acceptable limits of cost-effectiveness. Furthermore, it was shown that a longer time frame (5 or 10 years) leads to even more favourable cost-effective results. Conclusions Hydroxocobalamin appears cost-effective to dominant compared with standard treatment in CN poisoning from a healthcare payer's perspective.