The development of transgenic cotton cultivars gives cotton producers more options for controlling pests. The value of these cultivars to producers depends not only on the cost-savings that they may contribute to the pest management systems employed, but also on the gross revenues from the sale of the crop produced. This study examines the cost and returns associated with alternative pest control systems using transgenic and nontransgenic cultivars in an effort to identify the most economical alternatives. The experiments were done as holistic comparisons of production systems. The treatment variable was a specific combination of a cultivar and a pest management system that was consistent with the genetic potential of the cultivars. Over 5 site-years in Arkansas, yield was the factor most closely associated with profitability at each site in each year. In 3 of the 5 site-years, yields were not statistically different for most or all of the cultivars tested, so the least expensive treatment would also be the most profitable treatment. Comparisons among the cultivars tested in this research, indicate that the currently available cultivars offer ample opportunities to identify high-yielding cultivars and profitable systems within non-transgenic, insect-resistant, herbicideresistant, or combined insect- and herbicide-resistance (so-called “stack gene”) category of transgenic cottons.