ABSTRACTThe two present nomothetic studies focused on the period from 1996 to 2012 to determine relations between handedness and political orientation using the 48 contiguous American states as analytical units. The estimated percentage of left-handers in each state operationally defined handedness. A composite measure of Conservative-Republican preference was created from CBS/New York Times/Gallup polls of state resident conservatism and the percent in each state voting Republican in each presidential election from 1996 to 2012. Study 1 showed that state levels of left-handedness correlated to an extremely high degree with Conservative-Republican preference (r = −.80). As well, with common demographic differences between states reflected in socioeconomic status, White population percent, and urban population percent controlled through multiple regression, handedness still accounted for an additional 37.2% of the variance in Conservative-Republican preference. Study 2 found that each of the Big Five personality variables correlated significantly with handedness and with Conservative-Republican preference, but in the opposite direction. Furthermore, Study 2 demonstrated quite surprisingly that all Big Five personality relations to Conservative-Republican preference were eliminated when handedness was controlled in multiple regression equations. For all regression equations, the global Moran’s I test specifically developed for detecting residual spatial autocorrelation indicated no significant spatial autocorrelation.