Weed size can nfluence herbicide performance and herbicide interactions in mixtures. To control a broad range of species in soybean or cotton, POST herbicide mixtures will likely be commonplace in Roundup Ready® XtendFlex® and Enlist™ technologies. The impact of weed size on herbicide interactions that could occur in Roundup Ready XtendFlex or Enlist crops was assessed in two field experiments conducted in 2015 and 2016 at the Northeast Research and Extension Center in Keiser, AR. Combinations of glufosinate, glyphosate, dicamba, and 2,4-D were applied to either 10-cm or 30-cm weeds and evaluated for percent weed control, height reduction, and density reduction, collected 5 wk after treatment. Colby’s method was used to analyze treatments for herbicide interactions for control of barnyardgrass, Palmer amaranth, and pitted morningglory. Antagonism was identified with at least one treatment on all species. Almost all treatments were antagonistic for percent weed control, height reduction, and density reduction on barnyardgrass. When glyphosate in mixture with 2,4-D or dicamba was applied to 30-cm barnyardgrass, control declined 9% for both mixtures relative to glyphosate alone. Glufosinate plus glyphosate was antagonistic when applied to both 30-cm pitted morningglory and barnyardgrass. Glufosinate plus dicamba provided less control and density reduction of Palmer amaranth than what was expected from Colby’s equation. Overall, antagonism was more likely to be identified when applications were made to 30-cm weeds compared with 10-cm weeds. The utility of a given herbicide mixture will depend on the species present in the field and the size of those species at the time of application.