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The average life expectancy varies greatly from county to county in USA and there are also spatial variations in the county mortality rates for cardiovascular disease (CVD) and cancer, the top two causes of death. An association between these two groups of diseases has not been identified by cluster analysis previously. The main objective in this study was to investigate and quantify the associations between mortality due to CVD, cancer mortality and life expectancy based on US county data between 1980 and 2014. Regression analysis was used to adjust life expectancy for the mortality due to CVD and that due to cancer. In addition to the spatial life expectancy trends, we also studied existing trends over time with the software JOINPOINT to see how life expectancy is influenced by changes in mortality due to CVD and cancer mortality. The study setting was the 48 contiguous US states, while participants were 3,100 counties and their populations of all ages during the period 1980-2014. The main outcomes are spatial clusters of unusually low or high levels of life expectancy in addition to identifying which county level life expectancy locations were significantly associated with mortality due to CVD and/or cancer. Life expectancy has been improving steadily from 1980 to 2014, but the rate of increase per year (indicated by variation of the trend slope) changed significantly at five joinpoints, the latest of which occurred in 2010 when the slope changed from 0.29 (1980-1982) to 0.03 (2010-2014). Our results reveal that there are significant, purely spatial clusters in some geographical areas where life expectancy rates are significantly higher (or lower) than in the rest of the contiguous US. It is also shown that there is a significant association between the life expectancy level and the corresponding CVD mortality, and there is also a significant association between life expectancy level and the corresponding overall cancer mortality. The general trends (regression slopes) over time for the USA in life expectancy mortality, CVD mortality and cancer mortality have changed significantly after 2009-2010.