Background: The availability of an electronic radial scanning echoendoscope has facilitated the clinical use of tissue harmonic imaging. This study compares the quality of US images acquired by tissue harmonic imaging during electronic radial scanning EUS to those acquired by fundamental imaging. Methods: Electronic radial scanning EUS was performed in 108 patients with pancreatic lesions (58 cystic, 50 solid). US images acquired by fundamental imaging at a frequency of 7.5 MHz were compared with those acquired by tissue harmonic imaging by using transmitting and receiving frequencies of, respectively, 4.0 and 8.0 MHz at the same scanning plane. Cystic lesions were evaluated for boundary/septum and nodules, and solid lesions, for boundary and internal structure. US images acquired by tissue harmonic imaging and fundamental imaging during electronic radial scanning EUS were compared, by using a Likert scale for the respective evaluation criteria, by two independent endoscopists. Observations: For cystic lesions, tissue harmonic images were significantly clearer than fundamental images for visualizing boundary and septum (p < 0.0001, both reviewers) and nodules (p = 0.0003, Reviewer 1; p = 0.0007, Reviewer 2). For solid lesions, tissue harmonic images were significantly clearer than fundamental images for visualizing boundary (p = 0.0003, Reviewer 1; p < 0.0001, Reviewer 2) and internal structures (p = 0.0003, Reviewer 1; p = 0.0009, Reviewer 2). Conclusions: US images acquired by tissue harmonic imaging appear to be clearer compared with those acquired by fundamental imaging.