Objective: In this multicenter prospective study, we aimed to evaluate the use of holmium:yttrium–aluminum–garnet laser during retrograde intrarenal surgery for kidney stones and the relationship between laser-related parameters and procedure-related perioperative parameters. Material and methods: The 769 patients whose laser setting parameters (fiber thickness, number of shots, frequency (max.), laser power (max.), and total energy) were completely registered were included in this study program. The intraoperative ureteral lesions were evaluated using postureteroscopic lesion scale (PULS) scores and the postoperative complications with the modified Clavien-Dindo classification system. Results: The maximum levels of laser power and the frequency were used in the middle calyceal stones; the value of total energy consumed was found to be higher gain in cases with multiple stones (all parameters P <.05). There was a significant positive correlation among (mean number of shots [P <.001, r ¼ 0.46], frequency [P ¼.009, r ¼ 0.1], maximum power [P <.001, r ¼ 0.11], total energy [P <.001, r ¼ 0.25]), anesthesia time (P <.001, r ¼ 0.42), surgery time (P <.001, r ¼ 0.47), and stone size. The mean number of shots increased (P <.001, r ¼ 0.25), and the frequency level decreased (P <.001, r ¼ –0.17) significantly with increasing Hounsfield unit (HU) values. Again, the mean number of shots and maximum laser power increased in correlation with the increasing hospitalization time (P ¼.004, r ¼ 0.09 and P ¼.02, r ¼ 0.07, respectively). In addition, it was observed that higher laser subparameter values and thicker fibers were used in PULS grade 2. Conclusion: As the stone size and HU values increased, laser-setting parameters were found to show significant variability. The increase in different parameters of the laser setting was found to be associated with longer anesthesia time, surgery time, and hospitalization period and increased risk of local trauma with PULS grade.