Introduction: Laser lithotripsy during Mini-PCNL is one treatment option in urinary stone disease. In recent years, a new era in stone treatment has been initiated with the introduction of new pulsed thulium lasers. The aim of this study was to investigate the safety and efficacy of laser lithotripsy with a new pulsed solid-state thulium:YAG laser during mini-PCNL. Materials and methods: All patients, regardless of stone size, who were treated with a Mini-PCNL using the new pulsed thulium laser were prospectively enrolled. Operation times, stone size, laser time, and laser settings were noted. The stone-free rate was assessed postoperatively with sonography and either x-ray or computed tomography as a clinical standard. The complications were analyzed using the Clavien-Dindo classification. Results: A total of 50 patients with a mean age of 52 years were included. 31 (62 %) patients were male. The average stone size was 242.3 (±233.1) mm2 with an average density of 833 (±325) Hounsfield units. The mean operating time was 30.56 (±28.65) minutes, and the laser-on-time was 07:07 (± 07:08) minutes. The most commonly used settings were 0.4 J and 115 Hz (46 W). The mean total energy for stone ablation was 14,166 (±17,131) kJ. The total stone-free rate was 84 %, with an overall complication rate of 32% according to Clavien-Dindo (grade 1: n = 9, grade 2: n = 6, 3b: n = 1). In the group of patients with singular stones (n = 25), the stone-free rate was 88%. Summary: The new pulsed solid-state Thulium:YAG laser allows a safe and effective lithotripsy during Mini-PCNL. The stone-free rates were high regardless of stone size with a comparable low rate of complications.