To evaluate the association of preoperative noncontrast computed tomography stone characteristics, laser settings, and stone composition with cumulative holmium:yttrium-aluminum-garnet (Ho:YAG) laser time/energy. We retrospectively reviewed patients who underwent semirigid/flexible ureteroscopy and Ho:YAG laser lithotripsy (200 or 365 μm laser fiber; 0.8-1.0 J energy; and 8-10 Hz rate) at 2 tertiary care centers (April 2010-May 2012). Studied parameters were as follows: patient's characteristics; stone characteristics (location, burden, hardness, and composition); total laser time and energy; and surgical outcomes. One hundred patients met our inclusion criteria. Mean stone size was 1.01 ± 0.42 cm and volume 0.33 ± 0.04 cm(3). Mean stone radiodensity was 990 ± 296 HU, and Hounsfield units density 13.8 ± 6.0 HU/mm. All patients were considered stone free. Stone size and volume had a significant positive correlation with laser energy (R = 0.516, P <.001; R = 0.621, P <.001) and laser time (R = 0.477, P <.001; R = 0.567, P <.001). When controlling for stone size, only the correlation between HU and laser time was significant (R = 0.262, P = .011). In the multivariate analysis, with exception of stone composition (P = .103), all parameters significantly increased laser energy (R(2) = 0.524). Multivariate analysis revealed a positive significant association of laser time with stone volume (P <.001) and Hounsfield units density (P <.001; R(2) = 0.512). In multivariate analysis for laser energy, only calcium phosphate stones required less energy to fragment compared with uric acid stones. No significant differences were found in the multivariate laser time model. Ho:YAG laser cumulative energy and total time are significantly affected by stone dimensions, hardness location, fiber size, and power. Kidney location, laser fiber size, and laser power have more influence on the final laser energy than on the total laser time. Calcium phosphate stones require less laser energy to fragment.