We compared the impact of various energy settings, frequency, and fiber diameters on the stone fragmentation capabilities of the holmium laser. Stone phantoms, made from plaster of Paris and uniform in weight, were treated with one of two laser fiber sizes: small (200 and 365 microm) and large (550 and 1000 microm). Stones were immersed in water and fragmented for 3 minutes at 0.5, 1.0, or 2.0 J and 5, 10, or 15 Hz. The mean percentage decrease in weight in the two groups was compared using one-way ANOVA. The effect on flexible ureterorenoscope deflection of the small fibers was tested in two different ureterorenoscopes. Raising the energy level when using the small fibers resulted in more weight loss (P < 0.05). Increasing the frequency up to 10 Hz also resulted in a significant increase in weight loss (P < 0.05), yet above 10 Hz, there was no significant additional weight loss noted for either small fiber. There was no significant difference in the weight loss produced by the two fibers unless the energy setting was >1.0 J. Studies with the large fibers demonstrated similar results, with significant increments of weight loss occurring with increased energy (P < 0.05), while nonsignificant differences were seen for the two fiber diameters. Increasing laser frequency up to 15 Hz resulted in a significant increase in weight loss for the large fibers. Loss of ureterorenoscope deflection ranged from 7% to 16% and 18% to 37% for the 200-microm and 365-microm fibers, respectively. Small-diameter fibers, in combination with semirigid or flexible ureteroscopes, should be used to treat upper urinary tract stones. The 365-microm fiber should be utilized for the management of ureteral stones, as minimal endoscopic deflection is required to access these calculi. Because the 200-microm fibers are considerably more expensive, their use should be reserved for fragmentation of intrarenal calculi, where maximum deflection is required during flexible ureterorenoscopy. The ideal energy and frequency settings for the small fibers are <1.0 J and 5 to 10 Hz. Larger fibers can be used for managing bladder or renal calculi, as there is no need for significant fiber deflection. The 550-microm fiber is preferred, as it is comparable in efficacy to the 1000-microm fiber and is less expensive. Energy and frequency can be maximized to 2.0 J and 15 Hz without damage to the fiber, but visibility can be affected by high frequencies. Appropriate fiber selection and energy/frequency settings will allow access to most stones throughout the urinary tract, maximize fiber life, and minimize fiber expense.