Manual wheelchair propulsion (MWP) is an inefficient and physically straining process. A reliably fabricated and instrumented wheel can help researchers to accurately calculate the forces and moments exerted by the wheelchair users and propose strategies to improve MWP. In this study, an instrumented wheel is designed, fabricated, and validated by using general uncertainty analysis. A six-component transducer is used to measure three-dimensional forces and moments applied by the wheelchair user on the handrim. The output of the transducer are forces and moments, which are directly transmitted to a PC using a USB port. By developing the transformation equations, the actual forces and moments on the hand of the wheelchair user are calculated. The angular position of the hand on the handrim is calculated from the kinetic data obtained through the instrumented wheel, and the derived equations. The general uncertainty analysis method is used to calculate the uncertainty values for the variables of interest with the Taylor series expansions. An analysis of the results shows that it is possible to obtain reliable information for MWP by using the instrumented wheel. Most of the data have uncertainties under 5% during much of the propulsion phase, and the patterns and overall behavior of the results are comparable to published data.