We applied large eddy simulation (LES) to predict the course of reactive mixing carried out in confined impinging jet reactors (CIJR). The reactive mixing process was studied in a wide range of flow rates both experimentally and numerically using computational fluid dynamics (CFD). We compared several different reactor geometries made in different sizes in terms of both reaction yields and mixing efficiency. Our LES model predictions were validated using experimental data for the tracer concentration distribution and fast parallel chemical test reactions, and compared with the k-ε model supplemented with the turbulent mixer model. We found that the mixing efficiency was not affected by the flow rate only at the highest tested Reynolds numbers. The experimental results and LES predictions were found to be in good agreement for all reactor geometries and operating conditions, while the k-ε model well predicted the trend of changes. The CFD method used, i.e., the modeling approach using closure hypothesis, was positively validated as a useful tool in reactor design. This method allowed us to distinguish the best reactors in terms of mixing efficiency (T-mixer III and V-mixer III) and could provide insights for scale-up and application in different processes.