EUS associated with contrast-enhanced harmonic EUS (CH-EUS) and EUS elastography (EUS-E) are used in clinical practice to assess pancreatic tumor at the diagnosis. In case of pancreatic ductal adenocarcinoma (PDAC) with liver metastasis, nab-paclitaxel combined with gemcitabine is a first-line treatment option. We aimed to assess the modification of PDAC microenvironment induced by the combination of nab-paclitaxel with gemcitabine, by endoscopic ultrasonography techinics. This single center phase III study conducted between February 2015 and June 2016 included patients with pancreatic adenocarcinoma with mesurable liver metastasis and no prior cancer treatment fit for two cycles of nab-paclitaxel combined with gemcitabine. We aimed to perform EUS with CH-EUS and EUS-E of the pancreatic tumor, CT scan and contrast enhanced ultrasonogram (CE-US) of a reference liver metastasis, before and after the two cylces of chemotherapy. Primary end point was modification of vascularizaion of primary tumor and a reference liver metastasis. Secondary end points were modification of stromal content, safety profile of drug combination and tumor response rate. Sixteen patients were analyzed, but only 13 received two cycled of chemotherapy (CT) (toxicity [n = 1] or death [n = 2]). There was no statistical modification induced by CT concering vascularity of primary tumor (time to maximum intensity P = 0.24, value of maximum intensity P = 0.71, hypoechogenic aspect generated by injection of contrast enhancing agent), vascularity of a reference liver metastasis (time to maximum intensity P = 0.99, value of maximum intensity P = 0.71) and tumor elasticity (P = 0.22). Eleven patients had tumor response assessement, 6/11 (54%) had measurable disease response 4/11 (36%) with partial responses and 2/11 (18%) with stable disease. All other patients showed disease progression. No serious side effects occurred, 6/11 patients had a dose adjustment. We did not show significant modification of vascularity and elasticity but these results should be taken with caution because of important limitations.