Purpose: Among various intracorporeal lithotriptors, Lithoclast (EMS, Switzerland) has become the widely used tool for the treatment of urinary stones. Recently, the holmium:YAG laser has been used with a wide range of potential urological applications, including intracorporeal lithotripsy of urinary calculi. The purpose of the present study is to compare Lithoclast with holmium:YAG laser lithotripsy in ureteral calculi fragmentation. Methods: Out of 51 patients with ureteral calculi, 26 underwent Lithoclast lithotripsy and 25 holmium:YAG lithotripsy using a 8/9.8F rigid ureteroscope. There were no changes to the ureteroscopes, video monitors, baskets or irrigation devices during the study period. Results: There were no differences in patient age, sex, stone size and location of stones between these groups. The immediate stone-free rates were 96.0% in the holmium:YAG group and 73.1% in the Lithoclast group (P < 0.05). The 3-month stone-free rates were 96.0% and 84.6%, respectively (P = 0.350). The mean operation time and mean period of postoperative hospitalization in the holmium:YAG group (49.8 min and 1.0 days, respectively) were shorter than those of the Lithoclast counterpart (76.9 min and 2.5 days, respectively). Post-treatment complications, such as ureteral perforation, were encountered in only two patients who underwent Lithoclast. Conclusions: Holmium:YAG lithotripsy was associated with shorter operation time and postoperative hospitalization period. These data also suggest that holmium:YAG lithotripsy was safe and more effective than Lithoclast lithotripsy in the aspect of immediate stone free rate. We believe that holmium:YAG laser is an excellent treatment modality for managing ureteral calculi.