Purpose: We assessed the effectiveness and safety of holmium:YAG laser lithotripsy for managing upper urinary tract calculi in a prospective cohort of 598 patients. Materials and Methods: Ureteroscopic holmium:YAG laser lithotripsy was performed in 598 patients between 1993 and 1999. Calculi were located in the distal ureter in 39.6% of cases, mid ureter in 18.6%, proximal ureter in 32.4% and kidney in 9.4%. Patients were treated on an outpatient basis with various flexible and semirigid endoscopes. Of the cases 59% were referred as previous treatment failures. Patients were assessed 6 to 12 weeks postoperatively with repeat plain x-ray and ultrasound or excretory urography for late obstructive complications. Results: The overall stone-free rate was 97%. As stratified by location, the stone-free rate was 98% in the distal ureter, 100% in the mid ureter, 97% in the proximal ureter and 84% in the kidney. Fragmentation was incomplete in 6% of cases and secondary intervention was required in 6%. The overall complication rate was 4%. New onset ureteral stricture developed postoperatively in 0.35% of patients. Conclusions: Holmium:YAG laser lithotripsy is a highly effective and safe treatment modality for managing ureteral and a proportion of intrarenal calculi on an outpatient basis. The effectiveness and versatility of the holmium laser combined with small rigid or flexible endoscopes make it our modality of choice for ureteroscopic lithotripsy.