A large-plot study was conducted for five years to determine the effect of irrigation rate and fertigated nitrogen on the performance of Fibermax (FM) 989BR, Stoneville (ST) 5599BR, and Paymaster (PM) 2280 BG/RR in a field infested with the root-knot nematode (Meloidogyne incognita). The objective was to determine if irrigation rate would effect the relative ability of susceptible and root-knot nematode tolerant cultivars to perform in a root-knot nematode infested field. The split-plot design included irrigation and nitrogen rates as the whole plots (base irrigation rate = B, 75% of base rate [75%B], and 125% of base rate [125%B], with nitrogen applied through the center pivot system and being proportional to irrigation rate) and cultivars as the sub-plot with three replications. The B and 125%B rates had higher lint yield and gross loan value ha-1 (P < 0.05) than the 75%B rate when averaged across the three cultivars. The root-knot nematode tolerant cultivar ST 5599BR, averaged equal or higher lint yields than FM 989BR at all irrigation rates when averaged over five years. ST 5599BR and FM 989BR had similar gross loan values ha-1 at all three irrigation rates. ST 5599BR had higher lint yields and gross loan values ha-1 than PM 2280 BG/RR (2003 – 2006) at the B and 125%B rates. The Paymaster cultivar is susceptible to root-knot nematode. Increasing irrigation rate did not improve the profitability of susceptible cultivars in a root-knot infested field, compared to the response of a tolerant cultivar.