With the registration of pyraclostrobin (Headline) and azoxystrobin (Quadris) in the United States for protection of cotton (Gossypium hirsutum) foliage and bolls against fungal diseases, there has been increased interest in efficacy of the fungicides on mid- to late-season diseases and whether there are non-fungicidal plant health benefits. A total of 15 field trials were conducted throughout cotton growing regions of the United States between the 2008 and 2010 growing seasons. Applications of azoxystrobin and pyraclostrobin were made at the following rates and timings: 0.22 kg ai ha-1 at first bloom (FB); 0.11 kg ai ha-1 at FB with a sequential application being made 14-21 days later; and 0.11 kg ai ha-1 at FB with a second application (0.22 kg ai ha-1) 14-21 days later. Cotton height, total nodes, lint yield, and fiber quality parameters were used to compare treatments, which included a non-treated control. There were no significant treatment differences with respect to most parameters, including yield. Overall, disease pressure was low, but foliar symptoms, caused by Alternaria macrospora (3 tests in Jackson, TN), and Stemphylium solani + Cercospora gossypina (1 site in Statesboro, GA), were observed, as well as hardlock and boll rot in selected trials in Mississippi and Tennessee. It is concluded that application of fungicides in cotton should be based on disease risk and the potential of environmental conditions conducive for foliar disease development during the growing season.