Miscanthus x giganteus is a promising feedstock for cellulosic conversion to ethanol. High biomass yields and minimal fertilizer requirements have sparked widespread interest across the temperate region of the Eastern United States. It is important to evaluate the environmental effects of M. x giganteus under different soil types and climates before a possible cellulosic production system is established. The objective of our study was to monitor and examine the effects of M. x giganteus on soils under three different fertilization rates (0, 60, and 120 kg N/ha/yr), and across five different planting locations (Illinois, Nebraska, New Jersey, Virginia, and Kentucky). Specifically we evaluated soil moisture, nitrogen leaching, and biomass yields. We found N fertilization significantly increased both nitrate and ammonium leaching across all five of the sites. During the first three years of establishment N fertilization had no significant effect on plant height, tiller density, or dry biomass yield across all five sites, but increased harvested N in biomass. However, during the fourth year of M. x giganteus growth N fertilization was found to have a significant effect on dry biomass yield at the Illinois site. It is unclear if this increase in yield is a result of established M. x giganteus utilizing the applied N fertilizer, or a reflection of the severe drought that occurred in the summer of 2012. These data on multiple soil types and climates have allowed for a better understanding of the effects of N fertilization on M. x giganteus’ long term sustainability, and the range to which it is best suited.