To investigate the feasibility of readout-segmented diffusion-weighted (rsDW) magnetic resonance (MR) in assessing nerve invasion of soft tissue tumor. Forty-four patients with soft tissue mass in upper leg suspected of nerve invasion underwent rsDW MR. Nerve invasion by tumor was rated by 2 radiologists, respectively. Sensitivity and specificity of rsDW MR in identifying nerve invasion were calculated, with operation findings as reference of standard. Apparent diffusion coefficient and fraction of anisotropy of nerve were obtained using DW MR, and then were compared between invaded nerves and noninvasion cases. Inter-reader agreement in using rsDW MR to rate nerve invasion was excellent (kappa = 0.891 +/- 0.043, P < 0.001). Sensitivity and specificity of rsDW MR in identifying nerve invasion were 89% and 88%, respectively. Apparent diffusion coefficient was significantly higher in invaded nerves versus normal nerves (1.45 +/- 0.67 x 10(-3) mm(2)/s vs 1.39 +/- 0.46 x 10(-3) mm(2)/s, P < 0.05). Fraction of anisotropy was significantly lower in invaded nerves versus normal nerves (0.22 +/- 0.11 vs 0.37 +/- 0.13, P < .05). Readout-segmented DW MR was feasible in assessing sciatic nerve invasion by soft tissue tumor in selected patients.