Background Despite having influenza vaccination policies and programs, countries in the Americas underutilize seasonal influenza vaccine, in part because of insufficient evidence about severe influenza burden. We aimed to estimate the annual burden of influenza-associated respiratory hospitalizations in the Americas. Methods Thirty-five countries in the Americas with national influenza surveillance were invited to provide monthly laboratory data and hospital discharges for respiratory illness (International Classification of Diseases 10th edition J codes 0-99) during 2010-2015. In three age-strata (<5, 5-64, and .65 years), we estimated the influenza-associated hospitalizations rate by multiplying the monthly number of respiratory hospitalizations by the monthly proportion of influenza-positive samples and dividing by the census population. We used random effects meta-analyses to pool age-group specific rates and extrapolated to countries that did not contribute data, using pooled rates stratified by age group and country characteristics found to be associated with rates. Results Sixteen of 35 countries (46%) contributed primary data to the analyses, representing 79% of the America's population. The average pooled rate of influenza-associated respiratory hospitalization was 90/100,000 population (95% confidence interval 61-132) among children aged <5 years, 21/100,000 population (13-32) among persons aged 5-64 years, and 141/100,000 population (95-211) among persons aged .65 years. We estimated the average annual number of influenza-associated respiratory hospitalizations in the Americas to be 772,000 (95% credible interval 716,000-829,000). Conclusions Influenza-associated respiratory hospitalizations impose a heavy burden on health systems in the Americas. Countries in the Americas should use this information to justify investments in seasonal influenza vaccination-especially among young children and the elderly.