For most wild species affected by exotic pests or pathogens, the relative importance of heritable genetic differences in determining apparent variation in disease resistance is unknown. This is true in particular for butternut, a North American hardwood affected by butternut canker disease and undergoing demographic contraction. Little is known about site effects on butternut decline, in part because long-term monitoring data are lacking. We collected detailed disease phenotypes and multilocus microsatellite genotypes for all surviving individuals in a large natural population of butternut in 2003 (n= 302) and 2012 (n=113). Two analytical methods, correlations between pairwise phenotypic similarity and pairwise relatedness, and estimation of among-family variance, both indicated weak heritability of disease-related traits and no heritability for overall tree health in the population. Additionally, an analysis of spatial data collected in 2001 (n=341) and 2012 (n=113) demonstrated that drier, upland sites contribute to increased likelihood of survival. We conclude that genetic differences among wild butternut individuals contributed little to observed variance in survival over 10 years but fine-scale site differences were useful predictors of butternut mortality.