A newly designed and fabricated textile electromagnetic (EM) coupler and a novel side-by-side transmission coefficient measurement arrangement were found most suitable for clinical trial and practical implementation of a microwave-based system for monitoring vital signs and measuring changes in lung water content. Comparative simulation studies were conducted to determine the effect of the textile material’s conductivity on the sensitivity and accuracy of the new side-by-side measurement arrangement. Two sewing techniques were examined to develop a robust and stable textile EM coupler prototype with a secured feeding structure. The new textile EM couplers and measurement procedure are tested in human clinical studies. Results were benchmarked with an FDA-approved medical device and confirmed the readiness of the developed textile EM coupler and new side-by-side transmission coefficient measurement arrangement for clinical trials and the ultimate practical realization of this microwave technology. Specifically, it is shown that the embroidered steel thread textile EM coupler is best suited for practical implementation and provided high sensitivity to detect vital signs and a 1% change of lung water.