Comparative hydrodynamic loads caused by a focused wave acting on differently sized slender vertical cylinders placed in a wave canal were predicted at model scale using an unsteady Reynolds-averaged Navier–Stokes (URANS) solver and the Morison equation. This paper focused, first, on wake effects that need to be considered for the structural design of tripod configurations and, second, on the influence of these wake effects on wave-induced loads. For the Morison approach, flow velocities were gathered at incremental representative locations along the length of the cylinders, whereby the use of a central differencing approach obtained the associated flow accelerations. A first scenario dealt with a small- and a large-diameter cylinder, implemented individually at two immersion depths. A second scenario considered medium- and large-diameter cylinders arranged in a tripod configuration, where the upstream and downstream cylinders had the same diameter. For the single cylinder, impact loads obtained by both methods compared favorably to experimental measurements. For the tripod configuration, however, impact loads obtained by both methods differed due to the influence of wake effects. Thus, it was necessary to determine the influence of wake effects to assess the structural integrity of tripod configurations.