Recurrent epidemics of influenza are observed seasonally around the world with considerable health and economic consequences. A key quantity for the control of infectious diseases is the reproduction number, which measures the transmissibility of a pathogen and determines the magnitude of public health interventions necessary to control epidemics. Here we applied a simple epidemic model to weekly indicators of influenza mortality to estimate the reproduction numbers of seasonal influenza epidemics spanning three decades in the United States, France, and Australia. We found similar distributions of reproduction number estimates in the three countries, with mean value 1·3 and important year-to-year variability (range 0·9–2·1). Estimates derived from two different mortality indicators (pneumonia and influenza excess deaths and influenza-specific deaths) were in close agreement for the United States (correlation = 0·61, P<0·001) and France (correlation = 0·79, P<0·001), but not Australia. Interestingly, high prevalence of A/H3N2 influenza viruses was associated with high transmission seasons (P = 0·006), while B viruses were more prevalent in low transmission seasons (P = 0·004). The current vaccination strategy targeted at people at highest risk of severe disease outcome is suboptimal because current vaccines are poorly immunogenic in these population groups. Our results suggest that interrupting transmission of seasonal influenza would require a relatively high vaccination coverage (>60%) in healthy individuals who respond well to vaccine, in addition to periodic re-vaccination due to evolving viral antigens and waning population immunity.