It is difficult to assess the mortality burden of influenza epidemics in tropical countries. Until recently, the burden of influenza was believed to be negligible in Africa. We assessed the impact of the 2009 influenza epidemic on mortality in Madagascar by conducting Poisson regression analysis on mortality data from the deaths registry, after the first wave of the 2009 A(H1N1) virus pandemic. There were 20% more human deaths than expected in Antananarivo, Madagascar in November 2009, with excess mortality in the ≥50 years age group (relative risk 1·41). Furthermore, the number of deaths from pulmonary disease was significantly higher than the number of deaths from other causes during this pandemic period. These results suggest that the A(H1N1) 2009 virus pandemic may have been accompanied by an increase in mortality.