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Reliable estimates of the effectiveness of influenza vaccine among persons 65 years of age and older are important for informed vaccination policies and programs. Short-term studies may provide misleading pictures of long-term benefits, and residual confounding may have biased past results. This study examined the effectiveness of influenza vaccine in seniors over the long term while addressing potential bias and residual confounding in the results. Methods Data were pooled from 18 cohorts of community-dwelling elderly members of one U.S. health maintenance organization (HMO) for 1990–1991 through 1999–2000 and of two other HMOs for 1996–1997 through 1999–2000. Logistic regression was used to estimate the effectiveness of the vaccine for the prevention of hospitalization for pneumonia or influenza and death after adjustment for important covariates. Ad-ditional analyses explored for evidence of bias and the potential effect of residual confounding. Result