Optimization of a new system for organic solar cells is a multiparametric analysis problem that requires substantial efforts in terms of time and resources. The strong microstructure-dependent performance of polymer:polymer cells makes them particularly difficult to optimize, or to translate previous knowledge from spin coating into more scalable techniques. In this work, the photovoltaic performance of blade-coated devices was studied based on the promising polymer:polymer system PBDB-T and PF5-Y5 as donor and acceptor, respectively. Using the recently developed high-throughput methodology, the system was optimized for multiple variables, including solvent system, active layer composition, ratio, and thickness, among others, by fabricating more than 500 devices with less than 24 mg of each component. As a result, the power conversion efficiency of the blade-coated devices varied from 0.08 to 6.43 % in the best device. The performed statistical analysis of the large experimental data obtained showed that solvent selection had the major impact on the final device performance due to its influence on the active layer microstructure. As a conclusion, the use of the plot of the device efficiency in the Hansen space was proposed as a powerful tool to guide solvent selection in organic photovoltaics.