JAK2V617F-positive patients with essential thrombocythemia, as opposed to their mutation-negative counterparts, require lower doses of hydroxyurea (HU) for control of their platelet count. In the current study, we looked for predictors of HU response in 69 patients with primary myelofibrosis (PMF) and 56 with polycythemia vera (PV). JAK2V617F analysis was performed on bone marrow-derived DNA obtained at or near the time of diagnosis. HU response in PMF was associated with a shorter disease duration (P = 0.008), absence of previous therapy (P = 0.01), older age at diagnosis (P = 0.009), and presence of JAK2V617F (P = 0.02). On multivariable analysis, only the latter retained its significance (48% vs. 8% response in mutation positive vs. negative cases). In PV, JAK2V617F allele burden correlated directly with HU response (P = 0.05) and inversely with daily HU dose in responding patients (P = 0.02). The current study suggests that JAK2V617F presence identifies PMF patients who are likely to respond to HU therapy, and information on its allele burden helps in assigning the optimal starting dose in individual patients with PV.