Objective: To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) volume and apparent diffusion coefficient values (ADCs) for assessing lymph node metastases (LNM) and good response after chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC). Materials and methods: This retrospective study consisted of 61 patients with LARC who underwent pre- and post-CRT DW images. Two radiologists independently placed free-hand regions of interest in each tumor-containing section on DW images to calculate pre- and post-CRT tumor volume and tumor volume reduction rates (Δvolume). Regions of interest were drawn to include tumor on maximum cross-sectional slice to obtain ADCs. Areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate diagnostic performance in identifying LNM and good response after CRT using these parameters. Results: Inter-observer agreement and intra-observer agreement were excellent for pre- and post-CRT DW MR volume (intraclass correlation coefficient [ICC], 0.889–0.948) and moderate for pre- and post-CRT ADCs (ICC, 0.535–0.811). AUCs for identifying LNM were 0.508 for pre-CRT DW MR volume versus 0.705 for pre-CRT ADC, 0.855 for post-CRT DW MR volume versus 0.679 for post-CRT ADC, and 0.887 for Δvolume versus 0.533 for ΔADC. AUCs for identifying good response were 0.518 for pre-CRT volume versus 0.506 for pre-CRT ADC, 0.975 for post-CRT volume versus 0.723 for post-CRT ADC, and 0.987 for Δvolume versus 0.655 for ΔADC. Conclusion: DW MR Δvolume provided high diagnostic performance in discriminating LNM after CRT. DW MR Δvolume was equally as accurate as post-CRT DW MR volume for evaluating good response. Key Points: • Inter-observer agreement and intra-observer agreement were excellent for pre- and post-CRT DW MR volume (intraclass correlation coefficient [ICC], 0.889–0.948) and moderate for pre- and post-CRT ADCs (ICC, 0.535–0.811). • DW MR Δvolume provided high diagnostic performance in identifying LNM after CRT (AUC, 0.887) and good response (AUC, 0.987) and was significantly more accurate than pre-CRT DW MR volume (AUC, 0.508 and 0.518, respectively) and ADCs (AUC, 0.705 and 0.506, respectively). • DW MR Δvolume (AUC, 0.987) was equally as accurate as post-CRT DW MR volume (AUC, 0.975) for evaluating good response, while pre-CRT DW MR volume and ADCs were not reliable for evaluating LNM and good response after CRT (AUC, 0.506–0.723). © 2020, European Society of Radiology.