OBJECTIVE We aimed to prospectively determine if analyzing pre- and post-chemoradiotheraphy (CRT) changes in the signal intensity (SI) and apperent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI) can accurately predict complete responders for locally advanced rectal cancer. METHODS Thirty patients (mean age, 54.3 years) with locally advanced rectal cancer who underwent neoadjuvant CRT and subsequent surgery were included in this study. All patients were evaluated pre- and post-CRT by standardized turbo spin echo and DW-MRI. Pre- and post-CRT tumor and normal rectal wall SI (which were gradually scored as very high, high, intermediate, low, and no signal) and ADC values were recorded. RESULTS Tumor SIs were decreased in all of the patients that had a therapy response. However, complete tumor SI loss was only seen in two (22.2%) of nine patients with a pathological complete response, while it regressed to low and/or intermediate SI levels in the remaining seven patients (77.8%). Post-CRT ADC values of rectal tumors were significantly higher from the preCRT ADC values (P < 0.0001; Z=-9.39). However, post-CRT ADC values from the complete and partial/no response patient groups were not significantly different (P = 0.071; Z=-1.99). CONCLUSIONS In re-staging of rectal tumors by DW-MRI, an increase in ADC values and decrease in SIs can predict therapy response but cannot unequivocally determine a complete response.