© Wolters Kluwer Health, Inc. All rights reserved. Objectives The aim of this study was to test the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with concurrent perfusion phantom for monitoring therapeutic response in patients with pancreatic ductal adenocarcinoma (PDAC). Materials and Methods A prospective pilot study was conducted with 8 patients (7 men and 1 woman) aged 46 to 78 years (mean age, 66 years). Participants had either locally advanced (n = 7) or metastatic (n = 1) PDAC, and had 2 DCE-MRI examinations: one before and one 8 ± 1 weeks after starting first-line chemotherapy. A small triplicate perfusion phantom was imaged with each patient, serving as an internal reference for accurate quantitative image analysis. Tumor perfusion was measured with K trans using extended Tofts model before and after phantom-based data correction. Results are presented as mean ± SD and 95% confidence intervals (CIs). Statistical difference was evaluated with 1-way analysis of variance. Results Tumor-size change of responding group (n = 4) was-12% ± 4% at 8 weeks of therapy, while that of nonresponding group (n = 4) was 18% ± 15% (P = 0.0100). Before phantom-based data correction, the K trans change of responding tumors was 69% ± 23% (95% CI, 32% to 106%) at 8 weeks, whereas that of nonresponding tumors was-1% ± 41% (95% CI,-65% to 64%) (P = 0.0247). After correction, the data variation in each group was significantly reduced; the K trans change of responding tumors was 73% ± 6% (95% CI, 64% to 82%) compared with nonresponding tumors of-0% ± 5% (95% CI,-7% to 8%) (P < 0.0001). Conclusions Quantitative DCE-MRI measured the significant perfusion increase of PDAC tumors responding favorably to chemotherapy, with decreased variability after correction using a perfusion phantom.