Over a fourth of the cotton produced in the US since 2002 has been produced in Texas, with most coming from the High Plains. In recent years, Texas has accounted for almost half of all US cotton production (USDA-NASS, 2008b). Most cotton on the High Plains is of more storm-proof varieties that have traditionally been harvested using stripper harvesters. However, improvements in irrigation technology and shifting markets for US cotton have increased interest in picker harvesters in the region. A holistic comparison of picker and stripper harvesters in irrigated cotton on the High Plains of Texas was conducted focusing on differences in system efficiencies, the costs of ginning, fiber and yarn quality, and potential economic returns under comparable crop yields and conditions. Harvester performance was evaluated based on harvest efficiency, time-inmotion, and fuel consumption. Stripper harvesters left less cotton in the field, but most of the cotton left by the picker was of low quality. While the time spent in each operation of harvest was highly dependent on the operator and support equipment available, in general, picker harvesters were able to harvest a unit area of high-yielding cotton more quickly than stripper harvesters. The cost of ginning picked and stripped cotton was evaluated considering current fee schedules from gins on the High Plains. On average, it cost a producer $4.76 more per bale to gin stripped-and-field-cleaned cotton than picked cotton. Fiber quality parameters were compared between harvest treatments based on results from High Volume Instrument (HVI) and Advanced Fiber Information System (AFIS) tests. Samples were ring-spun into carded and carded-and-combed yarns. Differences in fiber quality between harvest treatments were more pronounced when growing conditions were less favorable. Few differences were detected in carded yarn quality between harvest treatments, while more pronounced differences favoring picked cotton were seen in carded-and-combed yarns. A cost-benefit analysis was conducted to determine the production scenarios in which picker and stripper harvesters were most appropriate. Results indicate that, if a producer has sufficient yields coupled with sufficient area to harvest per machine, picker harvesting is a more profitable alternative to producers of on the High Plains.