Abstract Background The Global Influenza Hospital Surveillance Network is an international platform whose primary objective is to study severe cases of influenza requiring hospitalization. Methods During the 2015–2016 influenza season, 11 sites in the Global Influenza Hospital Surveillance Network in nine countries (Russian Federation, Czech Republic, Turkey, France, China, Spain, Mexico, India, and Brazil) participated in a prospective, active-surveillance, hospital-based epidemiological study. Influenza infection was confirmed by reverse transcription-polymerase chain reaction. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza was estimated using a test-negative approach. Results 9882 patients with laboratory results were included of which 2415 (24.4%) were positive for influenza, including 1415 (14.3%) for A(H1N1)pdm09, 235 (2.4%) for A(H3N2), 180 (1.8%) for A not subtyped, 45 (0.5%) for B/Yamagata-lineage, 532 (5.4%) for B/Victoria-lineage, and 33 (0.3%) for B not subtyped. Of included admissions, 39% were