Large Eddy Simulation (LES) has already been widely applied for unsteady flow simulations (e.g., axial cascade simulation), showing its superiority in the case of turbulent flow fields. However, there are several obstacles in the practical use of LES as a cascade design tool for gas turbine engines. Several calculation parameters such as the inlet turbulence, spanwise extents, and many other boundary conditions, affect calculation results for LES simulation and can cause reliability problems. This study concentrates on investigating the effects of LES calculation parameters on the prediction of profile loss at high air inlet angle off-design condition. The LES flow field results were found to be sensitive to four parameters (i.e., inlet turbulence, spanwise domain extent, time step size, and outlet domain). The inlet turbulence affects the size of the laminar separation bubble, while the spanwise domain extent affects the velocity fluctuations of the wake in correspondence of the large-scale vortices shedding. The time step size affects the velocity fluctuations of the wake because of the number of times that the low-pass filter is applied. Finally, the outlet domain extent affects the whole calculation domain (from the leading edge to the wake). Overall, the results show that all four calculation parameters can change the flow characteristics, affecting the prediction of profile loss at off-design condition when using LES.