A new laboratory-based methodology for prediction of the maximum scour depth in cohesive soil has recently been developed at the University of South Carolina. Because of the absence of field data, a computational fluid dynamics model, FLUENT, is used to test the scale effects associated with such a methodology. The numerical model was first verified against measurements obtained in the laboratory. The numerical results agreed satisfactorily with the measurements. Then, the numerical model was applied to the rock island protecting the main piers of the Cooper River Bridge, located in Charleston, South Carolina. The scour hole created around the island in the laboratory was scaled up and used in the numerical model. The computed bed shear stresses compared satisfactorily with those scaled up from the measurements and the shear stress at which the field sample begins to erode. It was found that the scour depth of 3.7 m represents the equilibrium state, which is similar to the results scaled up from the laboratory experiments. The numerical results showed that the scour depth of 36 m calculated by the HEC-18 approach is significantly overestimated.