This research evaluated the profitability and N use efficiency of real time on-the-go optical sensing measurements (OPM) and variable-rate technologies (VRT) to manage spatial variability in cotton production in the Mississippi River Basin states of Louisiana, Mississippi, Missouri, and Tennessee. Two forms of OPM and VRT and the existing farmer practice (FP) were used to determine N fertilizer rates applied to cotton on farm fields in the four states. Changes in yields and N rates due to OPM and VRT were not enough to produce higher net returns and improve N use efficiency relative to the FP.