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Fungicides are commonly applied to control foliar fungal diseases of winter wheat in the central Great Plains of the United States and often are routinely recommended. However, economic benefits from fungicide application in winter wheat have rarely been quantified in this region. A total of eight field experiments were conducted in 2006 and 2007 in Nebraska, USA to quantify yield increases from fungicide applications to control foliar fungal diseases in winter wheat. Experiments were conducted at the same four locations (Mead, Clay Center, North Platte and Sidney) in both years. The fungicides used were azoxystrobin + propiconazole, pyraclostrobin, propiconazole, azoxystrobin and trifloxystrobin + propiconazole applied at varying rates and growth stages. Average wheat prices were calculated from data provided by the United States Department of Agriculture (USDA) Agricultural Marketing Service. Average fungicide and fungicide application costs were obtained through surveys of local retailers, chemical manufacturers and commercial applicators. These prices and costs were used to calculate net returns from fungicide treatments. The probability of a positive net return was 0.60, 1.00 and 0.80 in 2006 (dry, low disease severity), 2007 (wet, moderate to high disease severity) and both years combined, respectively. Net returns ranged from $−101 ha−1 to $172 ha−1 in 2006 and from $60 ha−1 to $294 ha−1 in 2007. Net returns were at least two times the total cost ($2 return on $1 investment) in 4 out of 60 or 6.7% of treatments in 2006 and 51 out of 60 or 85% of treatments in 2007. In 2006, the best net returns occurred at Mead and Clay Center and resulted from the treatments 1) azoxystrobin + propiconazole applied at Zadoks growth stage (GS) 31 (first node detectable) at a rate of 0.58 l ha−1 and 2) azoxystrobin + propiconazole applied at GS 31 at a rate of 0.58 l ha−1 and again at GS 37 (flag leaf just visible) at the same rate. In 2007, the treatments that resulted in the best net returns were 1) azoxystrobin + propiconazole applied at GS 39 (ligule/collar of flag leaf just visible) at a rate of 1.02 l ha−1, 2) pyraclostrobin applied at GS 39 at a rate of 0.66 l ha−1, 3) propiconazole applied at GS 39 at a rate of 0.29 l ha−1, and 4) trifloxystrobin + propiconazole applied at GS 39 at a rate of 0.73 l ha−1. For the same fungicide applied at the same rate at GS 31 and GS 39 in 2007 (wet, moderate to high disease severity), the GS 39 application generally resulted in a higher net return than the GS 31 application. Averaged across treatments and locations, net returns were $6 ha−1 and $183 ha−1 in 2006 and 2007, respectively. The results from this study indicate that foliar fungicide application to winter wheat can be profitable in years with moderate to high disease severity; however, net loss can result if fungicides are applied in years with low disease severity.