To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC).Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10–15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0–1000 s/mm 2 ) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change (∆ADC), and volume change (∆V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectal excision (pathologic complete response [pCR] vs. no pCR, ypT0–2 vs. ypT3–4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, ∆ADC, and ∆V for the detection of pCR was compared with receiver operating characteristics analysis.Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm 2 /s: 0.94 ± 0.12 × 10 −3 vs. 1.19 ± 0.22 × 10 −3 , p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: ΔV during : −62 ± 16 vs. −33 ± 16, respectively, p = 0.015; and ΔV post : −86 ± 12 vs. −60 ± 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the ΔV during and, respectively, 83% and 86% for the ΔV post . The ∆ADC during (ΔADC during ) and after RCT (ΔADC post ) showed a significantly higher value in patients with pCR compared with patients without (in %: ΔADC during : 72 ± 14 vs. 16 ± 12, p = 0.0006; and ΔADC post : 88 ± 35 vs. 26 ± 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the ΔADC during and, respectively, 100% and 93% for the ΔADC post .These initial findings indicate that DWI, using pretreatment ADC, ΔADC during , and ΔADC post may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements.