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Grain yields of winter wheat (Triticum aestivum L.) in the southern Great Plains are often reduced by the presence of foliar diseases. This study was conducted to determine whether the application of foliar fungicides is an economically optimal management strategy. The effects of fungicide treatment on commercially available hard red winter wheat varieties with differing levels of genetic resistance (i.e., resistant, intermediate, and susceptible) to foliar diseases were investigated at two locations, Apache and Lahoma, OK, USA, for the harvest years 2005–2012. Two fungicides were rotated between the two locations and applied at approximately Feekes growth stage 9–10.5. When averaged across years, plots to which fungicide was applied generated greater average net returns than plots that did not receive fungicide for susceptible varieties at Apache, and for resistant, intermediate, and susceptible varieties at …