Pneumatic lithotripsy (PL) and Ho: YAG laser lithotripsy (LL) are the most widely accepted methods in the endoscopic treatment of ureteral lithiasis. The objective is to compare efficacy and safety of pneumatic lithotripsy vs. Ho: YAG laser lithotripsy in the treatment of ureteral lithiasis.Prospective, single-blind, multicenter study. Adult patients were recruited from August 2017 to March 2019, in 23 institutions throughout Argentina. Patient demographics, stone characteristics, presence of double J stent prior to the intervention, stonefree rate (SF) and postoperative complications were evaluated and analyzed.A total of 366 patients with ureteral lithiasis were included, 204 in the PL group and 162 in the LL group. The SF rate was significantly higher in the LL group (77% vs. 92%), OR 3 .43 (1.76 to 6.70). The complication rate was significantly lower in the LL group (9.8% vs. 2.5%), OR 0.23 (0.07 to 0.71). In the multivariate analysis, the use of Ho: YAG energy, the location of the lithiasis in the distal ureter, and the preoperative placement of double J stent, were found to be predictors of SF status.Ho: YAG laser lithotripsy has a higher stone-free rate and a lower complication rate compared to pneumatic lithotripsy.