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To compare the effectiveness of oseltamivir for treatment of influenza A and influenza B, we conducted a prospective, multicenter study of the 2003-2004 and 2004-2005 influenza seasons. The study included 3351 patients in whom influenza had been diagnosed by use of an antigen detection test kit.Oseltamivir was administered to 1818 patients with influenza A and 1485 patients with influenza B. No anti-influenza drugs were administered to 21 patients with influenza A or to 27 patients with influenza B. Patients receiving oseltamivir therapy were divided into 4 groups according to the time between the onset of fever (temperature, ≥37.5°C) and administration of the first dose of oseltamivir (0-12 h, 13-24 h, 25-36 h, and 37-48 h). The patients were also divided into 4 subgroups on the basis of age (0-6 years, 7-15 years, 16-64 years, and >64 years). Virus isolation was performed after completion of oseltamivir therapy for 44 patients with influenza A and 31 patients with influenza B.The duration of fever was significantly shorter for patients with influenza A and B who were treated with oseltamivir than for patients who were not treated with an anti-influenza drug (P < .001 for both). The time until the patient became afebrile after the initial administration of oseltamivir and the duration of fever were significantly longer for patients with influenza B than for patients with influenza A for the 0-12 h, 13-24 h, 25-36 h, and 37-48 h groups (P < .001) and for all age groups (P < .001). After 4-6 days of oseltamivir therapy, the influenza B virus reisolation rate (51.6%) was significantly higher than the influenza A virus reisolation rate (15.9%) (P < .001).Oseltamivir is less effective for influenza B than for influenza A with regard to duration of fever and virus persistence, irrespective of patient age or the timing of administration of the first dose.