Increasing nitrogen use efficiency (NUE) and nitrogen response in winter wheat could help producers reduce input costs associated with nitrogen fertilizers and decrease the negative environmental impacts of N loss. The objectives of this research were to i) establish if there are genetic differences in NUE and other related parameters among wheat varieties commonly grown in the Great Plains, ii) determine if there are differences in N response among select varieties with a range of NUEs, and iii) determine if NUE influences N response. This information could be useful in future breeding efforts as researchers seek to develop more efficient varieties. This was approached by conducting two separate studies, a large NUE study with 25 winter wheat varieties, and a smaller N Rate study with 4 varieties that represented a range of NUEs based on the preliminary results of the NUE study. The NUE study was conducted over the course of several seasons and locations, with treatments of consisting of N Rate and variety. The experiment was laid out in a strip-plot design and replicated four times at each location. In the 2010-11 and 2011-12 seasons it was planted at the Kansas River Valley Experiment Field in Rossville, KS. In the 2012-13 season the experiment was planted at two locations, one at Silverlake and another at Ashland Bottoms, KS. The experiment was again planted at two locations in the fall of 2013, in Ashland Bottoms, KS, and Hutchinson, KS. The wheat varieties were grown with two N rates, 0 kg N ha−1 and 90 kg N ha−1. Nitrogen use efficiency was calculated as the grain yield per unit of available nitrogen (sum of soil N and fertilizer N) and ranged from 22-30 kg of grain per kg of N and was strongly influenced by variety with a p