The flow in exhaust diffusers along with the channel geometry strongly depends on the inflow conditions, including Mach number level, total pressure distribution, flow angle, and turbulence. In the first part of this paper, the impact of these parameters is analyzed using computational fluid dynamics, experimental data from the test rig, and field measurements. A widespread opinion is that the optimal condition for the diffuser is an axial uniform inflow. However, it is shown in this paper that nonuniform pressure distribution compared with a uniform one can lead to better diffuser performance and that a moderate residual swirl can improve the performance as well. In the second part of this paper, the minimization of exhaust losses in heavy-duty gas turbines is discussed and illustrated by two practical examples.