OBJECTIVES: White Blood Cell (WBC) monitoring in schizophrenic patients treated by Clozapine aims to prevent agranulocytosis. We assess the cost-effectiveness of WBC monitoring strategies based on three national regulations and an additional weekly short-run monitoring compared to the absence of monitoring. METHODS: A decision analytic model was built to perform a cost-utility analysis comparing distinct monitoring strategies from a health care perspective with a 3-year time horizon. Clinical and resources used parameters were based on national Clozapine patients’ registries, cohorts, and pharmacovigilance data; health-related quality of life and mortality estimates were derived from literature reviews. Robustness of results was challenged with one-way and probabilistic sensitivity analyses. RESULTS: Compared to the absence of monitoring, the number needed to treat of all strategies to avoid one death was 5,000. The gains in survival time adjusted on quality of life were less than 1 day, resulting in prohibitive incremental cost-effectiveness ratios (ICER) of at least 1 million USD per QALY gained,. The ICER increased with higher frequency and longer monitoring duration. The results remain robust in the one-way sensibility analyses and the probabilistic sensitivity analysis indicating that the absence of monitoring strategy has the highest probability of cost-effectiveness CONCLUSIONS: Long-run WBC monitoring based on current national detection guidelines is not cost-effective, even by unrealistically high agranulocytosis prevalence. New guidelines are needed to improve WBC monitoring in schizophrenic patients receiving Clozapine.