Transgenic cotton (Gossypium hirsutum L.) cultivars produce lint and seed and their propriety traits provide part of the crop’s insect management and/or enable use of broad-spectrum herbicides for weed management. The standard procedures for conducting official cultivar trials utilize common pest management across all cultivars; whereas the pest management options and their associated potential for cost reductions are principal features of current transgenic cultivars. Field experiments were conducted to compare production systems utilizing cotton cultivars possessing different transgenic technologies managed in accordance with their respective genetic capabilities. In 2001 and 2002, selection of the Roundup Ready (RR) technology system resulted in reduced returns to the producer, while higher returns were attained from nontransgenic, Bollgard (B), and Bollgard/Roundup Ready (BR) technologies. In 2003, selection of the RR technology system or the Bollgard II/Roundup Ready (B2R) system reduced returns, while similar, higher returns were attained from nontransgenic, B, and BR technologies. In 2004, a nontransgenic system was superior to the BR, B2R, and Liberty Link (LL) systems in Tifton, but similar returns were achieved from nontransgenic, BR, and B2R technologies in Midville. Cultivar selection was important among the technology systems. Collectively these results indicate that profitability was most closely associated with yields and not the transgenic technologies.