We present a self-consistent and three-dimensional quantum simulation for nanowire resonant tunneling diodes (RTDs) based on the Wigner transport equation with spatially dependent effective masses (SDEM), which is discretized by a third-order upwind difference scheme for high-accuracy calculation. Our calculation shows that the current density/voltage (J--V) characteristics of nanowire RTDs with a radius (R) < 5 nm largely deviate from those of the one-dimensional RTDs. As R decreases below 5 nm, the peak-to-valley ratio (PVR) of the low-V negative differential resistance (NDR) decreases rapidly, and the high- V NDR peak shifts sensitively to lower V and becomes sharper. In this study, these results are shown to be closely related to the SDEM. According to our analysis, the SDEM along the transport direction contributes to the formation of an ‘effective double barrier’ in the energy subbands that is higher than the double barrier expected by the band offset, and the SDEM along the confinement direction reduces the height of the effective double barrier. The performance of nanowire RTDs with R< 5 nm was proven to be highly dependent on R because of the SDEM along the confinement direction.