Glyphosate-tolerant and bromoxynil-resistant cotton (Gossypium hirsutum L.) give producers additional postemergence (POST) weed control options, but these technologies require producers to plan weed management practices in advance of planting the crop, thus increasing the complexity of the decision making process. The Herbicide Application Decision Support System (HADSS) is a computer program developed at North Carolina State University that is designed to help those confronted with making these decisions. The HADSS database from North Carolina was modified in 1999 to adapt it more closely to Oklahoma environmental conditions and cotton production systems. Seven field experiments were conducted in Oklahoma in 1999 and 2000 to validate those changes (i.e. to determine if HADSS can recommend POST treatments that are effective and economical in Oklahoma). HADSS treatments and results were compared with those made jointly by two Oklahoma State University weed scientists, designated as the “Expert”. Similar herbicides and herbicide combinations were recommended by HADSS and the Expert, and occasionally they were identical. Control of eight weed species was similar for the HADSS or the Expert treatments when they received the same preplant incorporated (PPI) and preemergence (PRE) herbicide regimes. Within systems with the same PPI or PRE herbicides, HADSS and the Expert treatments resulted in similar cotton lint yields in 42 of 46 possible comparisons (91%). HADSS treatments had higher yields in the other four (9%) comparisons. Adjusted net returns were not different between HADSS and Expert treatments in 38 of 46 possible comparisons (83%). HADSS treatments gave higher returns in the remaining eight (17%) comparisons; half were due to higher yields and half were attributable to lower herbicide costs. The results indicate the adapted program can aid decision making for efficient and economical POST herbicide applications in Oklahoma cotton.