The herbicide fluridone is a soil-residual herbicide that should provide effective control of several problematic agronomic weeds, but because of herbicide persistence, injury to rotational crops is possible. In this experiment, multiple rates of fluridone were applied PRE to cotton at four irrigated locations across Arkansas to determine the risk of fluridone persisting and injuring subsequently planted wheat, corn, soybean, rice, grain sorghum, and sunflower. The multiple rates of fluridone were compared with fluometuron and evaluated for percentage of crop injury, crop density, and potential yield loss for each crop at the end of the subsequent growing season. Regardless of the location, wheat exhibited the greatest injury with 13 to 26% at Fayetteville (silt loam), 8 to 15% at Pine Tree (silt loam), 2 to 7% at Keiser (silty clay), and 3 to 8% at Rohwer (silty clay). Along with high levels of injury to wheat, fluridone at 900 g ai ha−1 caused loss of wheat stands to 29 plants m−1 row compared with fluometuron, which had stands of 49 plants m−1 row. Although injury occurred in wheat at all locations, no rate of fluridone reduced wheat yields compared with fluometuron. Injury to grain sorghum ranged from 5 to 10% from all rates of fluridone at Pine Tree. Fluridone at 900 g ha−1 (11 plants m−1 row) also reduced grain sorghum stands at Pine Tree over that of fluometuron (19 plants m−1 row). A decrease in grain sorghum yield was also observed from fluridone at 448, 673, and 900 g ha−1 compared with fluometuron at Pine Tree. At Keiser, rice exhibited significant levels of injury (1 to 13%) from fluridone 393 d after treatment. In conclusion, injury to a wheat rotational crop is more likely following an application of fluridone in cotton than is injury to other rotational crops, but yield reductions are not expected for most rotational crops when fluridone is applied to cotton at an anticipated labeled rate of 224 g ha−1.