Objective. The aim was to evaluate diffusion-weighted imaging (DWI) as a tool for measuring treatment response in adolescents with enthesitis-related arthropathy (ERA). Methods. Twenty-two adolescents with ERA underwent routine MRI and DWI before and after TNF inhibitor therapy. Each patient's images were visually scored by two radiologists using the Spondyloarthritis Research Consortium of Canada system, and sacroiliac joint apparent diffusion coefficient (ADC) and normalized ADC (nADC) were measured for each patient. Therapeutic clinical response was defined as an improvement of 530% physician global assessment and radiological response defined as 52.5-point reduction in Spondyloarthritis Research Consortium of Canada score. We compared ADC and nADC changes in responders and non-responders using the Mann-Whitney-Wilcoxon test. Results. For both radiological and clinical definitions of response, reductions in ADC and nADC after treatment were greater in responders than in non-responders (for radiological response: ADC: P<0.01; nADC: P = 0.055; for clinical response: ADC: P = 0.33; nADC: P = 0.089). ADC and nADC could predict radiological response with a high level of sensitivity and specificity and were moderately sensitive and specific predictors of clinical response (the area under the receiver operating characteristic curves were as follows: ADC: 0.97, nADC: 0.82 for radiological response; and ADC: 0.67, nADC: 0.78 for clinical response). Conclusion. DWI measurements reflect the response to TNF inhibitor treatment in ERA patients with sacroiliitis as defined using radiological criteria and may also reflect clinical response. DWI is more objective than visual scoring and has the potential to be automated. ADC/nADC could be used as biomarkers of sacroiliitis in the clinic and in clinical trials.