As the electricity market has evolved with the addition of renewables to the generation mix, Heat Recovery Steam Generators (HRSGs) that were originally designed for base load conditions are now frequently forced to operate in a cycling and/or low-load regime. This can lead to front end tube-to header fatigue, creep or creep-fatigue failures, often induced by Gas Turbine (GT) flow imbalances causing locally-elevated tube temperatures and/or bending stresses on joints due to large temperature differences between tube rows. This paper focuses on the use of Computational Fluid Dynamics (CFD) as a tool to analyze the risks of shifting operation mode. Exhaust gas flow profiles were analyzed for various low load conditions in two power plants with differing vertical designs. One of the plants had already moved into cycling mode and suffered tube failures that were directly related to low-load (and start-up) exhaust flow patterns, the other plant is projected to operate in a frequent cycling mode in the near future. The contribution of CFD to identifying the conditions that lead to failure for the first plant is presented, along with projections on the potential impact of lowload operation on the second plant design in terms of risk of hotend tube failures. Mechanisms to reduce the failure risk, such as addition of flow-conditioning devices, are also investigated.