Flupyradifurone is a systemic insecticide developed by Bayer CropScience that protects crops from sap-feeding pests like aphids and whiteflies. Flupyradifurone was approved for use in plant protection products by the EU in 2015, and extensive experimental polymorph screening was performed by Bayer during the product development. The Schrodinger team were provided with only the 2D structure of flupyradifurone and performed polymorph predictions without any experimental data. Upon completion of the presented CSP workflow, prediction results were sent to Bayer to compare with the experimental polymorph screening results. The predictions were limited to Z'=1 space due to the current limitation of the method. The predicted polymorph landscape in Z'=1 space is shown in Figure . Using r 2 SCAN-D3, flupyradifurone has a very dense energy landscape with 42 predicted structures within the lowest 2.0 kcal/mol energy window. The lowest energy predicted structure matches very well with the only known Z'=1 experimental structure Mod I (RMSD32 of 0.12Å between predicted and experimental structure as shown in Figure (e)), and simulated PXRD also agrees well with the experimental spectra (Figure (f)). In addition to Mod I, flupyradifurone also has a Z'=2 experimental structure (Mod II) that was not attempted in the current round of calculations. We also performed free energy calculations of the top predicted Z'=1 structures along with the Z'=2 experimental Mod II to obtain their relative stabilities as a function of temperature. As shown in Figure (g), according to the calculations, the lowest energy predicted structure at 0K (corresponding to experimental Mod I) is most stable at all temperatures below 400K. These results are consistent with Bayer's experimental findings that Mod II and Mod I are monotropic polymorphs with Mod I more stable at all temperatures below its melting point of 361K.