The efficacy of influenza vaccination is not well understood for major cause-specific mortality except pneumonia. For 10 months we followed the mortality data of 35,637 vaccinated elderly (>65 years old) in a county with 102,698 elderly in southern Taiwan. A multivariate Cox model showed that vaccination was significantly associated with lower mortality for all causes, [hazards ratio (HR)=0.56], stroke (HR=0.35), renal disease (HR=0.40), diabetes mellitus (HR=0.45), pneumonia (HR=0.47), COPD (HR=0.55), malignancy (HR=0.74), and heart diseases (HR=0.78), p<0.05. Influenza vaccination was strongly associated with reducing major cause-specific mortality.