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Abstract Introduction: Polycythemia vera (PV) is a rare myeloproliferative neoplasm (MPN) characterized by elevated red blood cell production and associated with an increased risk of thromboembolic events, as well as potential progression to myelofibrosis or acute myeloid leukemia. Current treatment approaches for PV follow risk-adapted guidelines from the National Comprehensive Cancer Network (NCCN) and the European Leukemia Net (ELN), which stratify patients into high-risk and low-risk categories. This study aimed to estimate the number of incident and prevalent PV patients eligible for treatment per NCCN guidelines across major U.S. health plans. Methods: The literature was reviewed systematically to identify epidemiological estimates of prevalence and incidence of PV, determine the distribution of NCCN/ELN risk classifications, and assess eligibility for NCCN 1.2025-recommended cytoreductive therapies. Membership data for the eight largest U.S. commercial health plans were extracted from earnings releases, annual reports, and 10-K filings. These data were incorporated into Microsoft Excel to develop model inputs and calculate the base-case estimates of patients clinically eligible for NCCN-recommended therapies. Results: Nine sources were identified to provide data on PV epidemiology, ELN/NCCN risk classification distribution, and utilization of NCCN-recommended therapies through separate systematic searches. A mean of 1.17 (SD ± 0.29) incident and 50.94 (SD ± 5.01) prevalent polycythemia vera (PV) patients per 100,000 individuals were identified through literature. Across the eight health plans analyzed, the mean and median covered lives were 38,725,462 and 27,847,800, respectively. Among these health plans, an average of 453 (SD ± 385) incident and 19,728 (SD ± 16,771) prevalent PV patients were calculated. Of these, a mean of 323 (SD ± 274) incident high-risk and 14,057 (SD ± 11,949) prevalent high-risk PV patients were identified. The proportion of patients using cytoreductive therapy was 37.3%, corresponding to an average of 169 (SD ± 144) incident and 7,354 (SD ± 6,252) prevalent patients.Conclusion: There is significant variability in the estimates of both incident and prevalent PV populations eligible for NCCN-recommended cytoreductive therapies across U.S. commercial health plans, which may influence formulary policy decisions.