Developing best practices for nitrogen (N) management is a “moving target” and requires continuous and coordinated research and Extension efforts. However, many research trials focus solely on cotton yield and quality and do not account for variations in soil type, environmental conditions, cropping systems (tillage, rotation, tillage, cover crop, etc.), irrigation, and preplant residual nitrates. Because of this exclusive focus on N rate, the vast majority of trials provide confounding results and do not identify the optimum rate that should be applied on a given farm with a specific soil type and cropping system. This presentation reports results of a multistate project started in 2020 to improve understanding of soil biophysical properties in predicting cotton yield and quality response to N application rate. Nitrogen rate response trials were established using different N rates. Rates and sites were selected based on the local conditions and history of previous positive cotton yield responses to N applications. In 2020, at 10 of 22 sites, lint yield responded nonsignificantly to N applications. These sites had large variations in lint yield, with the mean site yield varying from 445 to 1,451 lbs./acre. At the other 12 sites, a quadratic, curvilinear, or linear plus plateau response of lint yield to N applications was observed, and the profit-maximizing N rate at these sites varied from 31 to 136 lbs./acre. The N factor (lbs. N/lb. lint) varied from 0.03 to 0.20 across sites. The results from this study warrant including information from soil biophysical properties in making N recommendations to determine where to apply N and how much to apply. Following the revised N guidelines will help to increase farm profits and improve the environmental sustainability of cotton production.