Abstract The Hessian fly, Mayetiola destructor (Say) (Diptera: Cecidomyiidae), is a potentially severe pest of wheat, Triticum aestivum L. em Thell, in the southeastern United States. Plant resistance is an effective method to control Hessian fly, but when adapted high-yielding varieties with effective resistance are not available, neonicotinoid insecticide seed treatments may provide an alternative method of control of Hessian fly on susceptible varieties of winter wheat. A series of experiments were conducted to examine the efficacy of neonicotinoid seed treatments for control of Hessian fly in winter wheat. Infestations and immature numbers per tiller were assessed during the vegetative stages in autumn and winter and the wheat reproductive stage during the spring. Both imidacloprid 480FS at 0.31 g active ingredient (a.i.)/kg of seed and clothianidin at 0.39 g a.i./kg or higher rates provided consistent reductions in Hessian fly infestations during autumn and early winter. Lower rates were less effective, and they did not provide consistent reductions in autumn infestations. Thiamethoxam was evaluated at one rate in two experiments and was similar in efficacy to imidacloprid and clothianidin at the same rate. None of the seed treatments provided effective control of spring infestations during the wheat reproductive stage. Imidacloprid and clothianidin at rates of 0.31 g a.i./kg of seed or higher rates had a positive yield response in eight of nine comparisons, with an average increase of 285.9 ± 92.7 kg/ha. Neonicotinoid insecticide seed treatments at higher rates provide a useful method for managing Hessian fly on susceptible varieties of winter wheat.