The objectives of this study are to assess the efficacy and safety of retrograde ureteroscopic holmium laser lithotripsy for intrarenal calculi greater than 2 cm in diameter. A total of 24 patients with a stone burden >2 cm were treated with retrograde ureteroscopic laser lithotripsy. Primary study endpoints were number of treatments until the patient was stone free and perioperative complications with a follow-up of at least 3 months after intervention. In 24 patients (11 women and 13 men, 20-78 years of age), a total of 40 intrarenal calculi were treated with retrograde endoscopic procedures. At the time of the initial procedure, calculi had an average total linear diameter of 29.75 ± 1.57 mm and an average stone volume of 739.52 ± 82.12 mm(3). The mean number of procedures per patient was 1.7 ± 0.8 (range 1-3 procedures). The overall stone-free rate was 92%. After 1, 2 and 3 procedures 54, 79 and 92% of patients were stone free, respectively. There were no major complications. Minor postoperative complications included pyelonephritis in three cases (7.5%), of whom all responded immediately to parenteral antibiotics. In one patient the development of steinstrasse in the distal ureter required ureteroscopic fragment disruption and basketing. Ureteroscopy with holmium laser lithotripsy represents an efficient treatment option and allows the treatment of large intrarenal calculi of all compositions and throughout the whole collecting system even for patients with a stone burden of more than 2 cm size.