Background: Antiviral drugs are critical adjuncts to influenza vaccination. This study determined the in vitro susceptibilities of influenza A and B viruses isolated in the 2010-2011 season in Russia to the neuraminidase inhibitor oseltamivir and the hemagglutinin fusion inhibitor umifenovir and clinical efficacy of this antiviral drugs in this season. Methods: The antiviral potency of these drugs against A(H1N1)pdm09 virus in mice was assessed. Importantly, the clinical effectiveness of oseltamivir and umifenovir was evaluated in a retrospective study conducted in 26 regions of Russia. Results: All tested viruses (n= 36) were susceptible to oseltamivir and umifenovir in vitro. Oseltamivir (10. mg/kg/day) and umifenovir (60 mg/kg/day) significantly increased the survival of mice challenged with A/California/04/2009 (H1N1)pdm09 virus (p< 0.05). Influenza infection was laboratory-confirmed in 442 patients among 1462 patients hospitalized with acute respiratory infections. The treatment of influenza-infected patients within 48 h of symptom onset with oseltamivir and umifenovir was associated with a significant decrease in the duration of illness (2-3 days) and symptoms (p< 0.001). Pneumonia was observed in none of the patients treated with oseltamivir and in 0.3% of the patients treated with umifenovir, compared to 23.7% of patients who did not receive antiviral therapy (p< 0.001). Conclusions: This study provided experimental and clinical evidence of the efficacy of oseltamivir and umifenovir against influenza viruses, representatives of which have continued to circulate in post-pandemic seasons. © 2016 The Authors.