BACKGROUND: The mortality burden of the 2009 A/H1N1 influenza pandemic remains controversial, in part because of delays in reporting of vital statistics that are traditionally used to measure influenza-related excess mortality. Here, we compare excess mortality rates and years of life lost (YLL) for pandemic and seasonal influenza in Mexico and evaluate laboratory-confirmed death reports. METHODS: Monthly age- and cause-specific death rates from January 2000 through April 2010 and population-based surveillance of influenza virus activity were used to estimate excess mortality and YLL in Mexico. Age-stratified laboratory-confirmed A/H1N1 death reports were obtained from an active surveillance system covering 40% of the population. RESULTS: The A/H1N1 pandemic was associated with 11.1 excess all-cause deaths per 100,000 population and 445,000 YLL during the 3 waves of virus activity in Mexico, April-December 2009. The pandemic mortality burden was 0.6-2.6 times that of a typical influenza season and lower than that of the severe 2003-2004 influenza epidemic. Individuals aged 5-19 and 20-59 years were disproportionately affected relative to their experience with seasonal influenza. Laboratory-confirmed deaths captured 1 of 7 pandemic excess deaths overall but only 1 of 41 deaths in persons >60 years of age in 2009. A recrudescence of excess mortality was observed in older persons during winter 2010, in a period when influenza and respiratory syncytial virus cocirculated. CONCLUSIONS: Mexico experienced higher 2009 A/H1N1 pandemic mortality burden than other countries for which estimates are available. Further analyses of detailed vital statistics are required to assess geographical variation in the mortality patterns of this pandemic.