The shear wave velocity ( V S ) structure of the deep sediments in the Mississippi embayment is of interest to engineers and seismologists due to its influence on seismic wave propagation and site response during an earthquake. Although the shallow V S structure (top 30 to 60 m) is generally well characterized, information on the V S structure at greater depths (to 1000 m in some regions) is very limited. Past studies have developed relationships between the average V S ( V S,AVE ) of post-Paleozoic sediments in the embayment as a function of sediment thickness. One of these studies used converted body wave arrivals while the other used ambient noise measurements processed with the Horizontal-to-Vertical Spectral Ratio (HVSR) method. Interestingly, these two approaches yielded relationships that differed by about 25% to 30%. The objective of this study is to investigate the cause of the discrepancy between these relationships and identify the more reliable relationship for the V S structure in the Mississippi embayment. Experimental measurements of ambient noise were performed at eleven deep soil sites in the Mississippi embayment and analyzed using the HVSR method. The results from the experimental study yielded V S,AVE values that were consistent with findings from the previous HVSR study. However, simulations of body and surface wave propagation performed using estimated full-depth V S profiles at each site showed that the methodology used to develop the velocity–thickness relationship, specifically the approximate relationship used to relate site frequency, sediment thickness and V S , produces an overestimation of the true V S,AVE for the profile by 25 to 30%.