OBJECTIVE To evaluate the value of endoscopic ultrasonography (EUS) in the choice of endoscopic therapy strategies for mesenchymal tumors of the upper gastrointestinal tract. METHODS From July 2004 to September 2010, 1050 patients with upper gastrointestinal mesenchymal tumors (GIMTs) were diagnosed using EUS. Among them, 201 patients underwent different endoscopic therapies based on the deriving layers, growth patterns and lesion sizes. RESULTS Using EUS, we found 543 leiomyomas and 507 stromal tumors. One hundred and thirty-three leiomyomas and 24 stromal tumors were treated by snare electrosection, 6 leiomyomas and 20 stromal tumors were treated by endoloop, 10 stromal tumors were treated by endoscopic mucosal resection and 8 stromal tumors were treated by endoscopic submucosal dissection. Complete resection of the lesion was achieved in all cases. Of the mesenchymal tumors, 90.38% diagnosed by EUS were also identified by pathohistology. All wounds were closed up nicely and no recurrence was found in the follow-up after 2 mo. CONCLUSIONS EUS is an effective means of diagnosis for upper GIMTs and is an important tool in choosing the endoscopic therapy for GIMTs, by which the lesions can be treated safely and effectively.