The lack of adequate equipment and measurement tools in whole-body vibration has imposed significant constraints on what can be measured and what can be investigated in the field. Most current studies are limited to single direction measurements while focusing on simple postures. Besides the limitation in measurement, most of the current biomechanical measures, such as the seat-to-head transmissibility, have discrepancies in the way they are calculated across different labs. Additionally, this field lacks an important measure to quantify the subjective discomfort of individuals, especially when sitting with different postures or in multiple-axis vibration. This work begins by explaining discrepancies in measurement techniques and uses accelerometers and motion capture to provide the basis for more accurate measurement during single- and three-dimensional human vibration responses. Building on this concept, a new data collection method is introduced using inertial sensors to measure the human response in whole-body vibration. The results indicate that measurement errors are considerably reduced by utilizing the proposed methods and that accurate measurements can be gathered in multiple-axis vibration. Next, a biomechanically driven predictive model was developed to evaluate human discomfort during single-axis sinusoidal vibration. The results indicate that the peak discomfort can be captured with the predictive model during multiple seated postures. The predictive model was then modified to examine human discomfort to whole-body vibration on a larger scale with random vibrations, multiple postures, and multiple vibration directions. The results demonstrate that the predictive measure can capture human discomfort in random vibration and during varying seated postures. Lastly, a new concept called effective seat-to-head transmissibility is introduced, which describes how to combine the human body's biodynamic response to vibration from multiple directions. This concept is further utilized to quantify the human response using many different vibration conditions and seated postures during 6D vibration. The results from this study demonstrate how complicated vibrations from multiple-input and multiple-output motions can be resolved into a single measure. The proposed effective seat-to-head transmissibility concept presents an objective tool to gain insights into the effect of posture and surrounding equipment on the biodynamic response of the operators. This thesis is timely as advances in seat design for operators are increasingly important with evolving armrests, backrests, and seat suspension systems. The utilization of comprehensive measurement techniques, a predictive discomfort model, and the concept of effective seat-to-head transmissibility, therefore, would be beneficial to the fields of seat/equipment design as well as human biomechanics studies in whole-body vibration.