Background Since definitive concurrent chemoradiotherapy (CRT) is standard therapy for inoperable esophageal squamous cell carcinoma (ESCC), early evaluation of treatment response is crucial for patients and would be useful in assessing response, especially in patients with severe side effects. Purpose To explore the feasibility of intravoxel incoherent motion (IVIM) MRI in the early assessment of treatment response to CRT. Study Type Prospective. Population Twenty-three inoperable ESCC patients. Sequence IVIM 3T MRI of nine b values (0, 25, 50, 75, 100, 150, 200, 500 and 800 s/mm 2 ) was performed at four timepoints: pre-CRT (within 5 days before CRT), mid-CRT (2–3 weeks after the start of CRT), end-CRT (within 5 days after the end of CRT), and post-CRT (1 month after the end of CRT). Assessment IVIM-based parameters and ADC were analyzed independently by two radiologists and treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Statistical Tests Analyses of variance for repeated measurements were conducted to observe dynamic changes of IVIM-based parameters (D, f, and D*) and ADC during CRT. The parameters and their change percentages (Δ%) were compared between complete response (CR) and partial response (PR) by Mann–Whitney U -test. Diagnostic performance of parameters in predicting response was tested with receiver-operating characteristic curve analysis. Results ADC, D, and f increased significantly during CRT ( P 〈 0.001, 〈 0.001, and 0.001, respectively). ADC, f, Δ%ADC, and Δ%D at mid-CRT in CR group were significantly higher than those in the PR group ( P = 0.002, 0.013, 0.005, and 0.011, respectively). D combined with f and ADC had highest area under curve (0.917) in identifying CR from PR. Data Conclusion IVIM parameters proved useful in assessing response to definitive concurrent CRT for inoperable ESCC and combined with ADC at an early stage of treatment was a good predictor of response. Level of Evidence : 2 Technical Efficacy : Stage 4 J. Magn. Reson. Imaging 2018.