Frogeye leaf spot (FLS), caused by Cercospora sojina, is an economically important disease of soybean in many parts of the world where soybean is grown, including the United States. A meta-analytic approach was used to summarize a data set of 66 uniform field research trials conducted to evaluate fungicide efficacy against FLS on soybean. The dataset spanned 10 years (2012 to 2021) of experiments conducted across eight states in the U.S., including Alabama, Arkansas, Illinois, Iowa, Kentucky, Louisiana, Mississippi and Tennessee. First, the relationship between FLS severity and soybean yield was investigated. A significant negative slope obtained through random effects meta-analytic models confirmed the negative linear relationship between FLS severity and soybean yield. Additionally, the overall relative damage coefficient was calculated to be 0.51%. In addition, economic damage thresholds were estimated by using the damage coefficient, for a range of soybean prices and control costs, taking into account three different fungicide efficacies (25%, 50% and 75%). The threshold values increased as the control efficacy also increased and were affected by different crop prices and fungicide costs. Second, the best fungicide options to control the disease were investigated. The results demonstrated that fungicide efficacy against FLS differ among active ingredients and is decreasing over time possibly due to fungicide resistant populations (mainly to the quinone outside inhibitors [QoIs]). The best performing fungicide reported in this study was a mixture of difenoconazole + pydiflumetofen, and the poorest performing fungicide was pyraclostrobin, a QoI fungicide. A statistically significant (P<0.05) decline in performance was detected for two fungicide mixtures (azoxystrobin + difenoconazole and thiophanate-methyl + tebuconazole) and two single active ingredients (pyraclostrobin and tetraconazole). Greater yields in trials with conditions favorable for severe epidemics were found, which could be explained by the more evident effect of the fungicides among the treated plots when compared to the nontreated control. Accordingly, the most effective treatments were more likely to be profitable under higher disease pressure and, as expected, the less effective treatment reported the higher risk of not offsetting the costs. Third, the profitability of applying fungicides was investigated in the absence or very low levels of FLS in double-crop soybean by using a different data set of 22 fungicide trials conducted between 2008 and 2021 across five states in the U.S. (Illinois, Indiana, Kentucky, Missouri, and Tennessee). The results showed no significant difference in yield response between the fungicide treatments and the nontreated control. Economic analyses indicated that, due to the lower yield responses, probabilities of breaking even were less than 50% for all the single fungicide classes, or up to 51% for mixtures, depending on fungicide cost and soybean price values. Overall, these research findings may provide useful information for regional risk assessment of potential yield loss caused by FLS, and for planning fungicide programs to control this important foliar disease. Decisions on fungicide planning must take into account, not only technical information such as control efficacy and yield return, but also profitability and strategies to mitigate fungicide resistance issues. Keywords: Cercospora sojina. Chemical control. Economic risk. Fungicide. Glycine max. Yield loss.