The aim of the present study was to analyze the mortality trend due to ischemic heart disease (IHD) among older adults, identify changes in the trend and determine the correlation with influenza vaccine coverage (2000 to 2012) in the state of São Paulo between 1980 and 2012. An ecological time series study was conducted involving secondary data from Brazilian information systems. Linear and polynomial regression models as well as joinpoint regression were used to estimate the trends. Pearson's correlation coefficient was used to evaluate the correlation between age-standardized mortality coefficients and vaccine coverage. A decreasing tendency in mortality due to IHD occurred in both sexes, higher mortality rates were found for males and greater reductions were found in the period after the vaccination campaigns. However, no statistically significant changes occurred in the year coinciding with or near the onset of the campaigns. In the overall sample, no evidence of a linear correlation was found between the mortality coefficients and vaccination coverage. Other factors directly associated with morbidity and mortality due to ischemic heart disease may have influenced the trend.