In 1993 Sayer et al. reported the ex vivo results of the 2100 nm holmium:YAG (Ho:YAG ) laser for use in the setting of lithotripsy [17]. Ho:YAG presented as an ideal candidate to perform laser lithotripsy due to the ability of applying laser energy through small, flexible quartz fibers. Interesting experiments were performed on ureter specimens obtained at the time of radical nephrectomy for renal cell carcinoma. The stones were placed in the ureters and laser lithotripsy was performed with ureteroscopic delivery of the laser via a 400 μ fiber monitored by video. Stones of several different compositions were used with the laser set to 5 Hz and 0.5 J/pulse, and the total energy to complete stone fragmentation was recorded (Table 9.1). It was noted that lithotripsy was reasonably effective for all stone compositions tested. The frequency and power settings were then increased in a stepwise manner, and lithotripsy was performed at increasingly higher settings. Ureteric specimens were sent to pathology after completion of lithotripsy, and results were recorded (Table 9.2). Finally, the ureters were intentionally perforated at varying settings, and these pathology results were also recorded as well as the time to ureteral perforation (Table 9.3). It was noted that settings of 5 Hz with 0.5 J/s were safe settings, but ureteric injury occurred at higher power and frequency settings. These injuries many times were not visible on ureteroscopy. Coagulative necrosis was noted at the site of injury although the mechanism for lithotripsy of the holmium:YAG laser was at the time thought to be the same as the pulsed dye lasers, namely throught the generation of acoustic shockwaves (Fig. 9.2). It was later shown that Ho:YAG laser mechanism of fragmentation was through the generation of thermal energy [18]. The Ho:YAG laser has a significantly longer pulse duration than the pulsed coumarin dye laser (250–350 μs vs 1 μs), and that difference along with the observation of the effect of high temperatures led Vasssar et al. to question the proposed mechanism of laser-induced shockwave lithotripsy (LISL), as had been shown with the flashpump pulsed dye laser (Fig. 9.2). Experiments similar to those conducted in 1987 were performed which demostrated lithotripsy occurring prior to the development of a shockwave from collapse of the vapor bubble, no significant pressure generated from the Ho:YAG laser with a pulse length of 250 μs, and no significant lithotripsy occuring when the incidence angle of the laser was 90° in relation to the stone despite adequate contact with the vapor bubble. In addition, lithotripsy was more effective when stones were dry and carried out in air and when the stone temperature started at 20 °C as opposed to −80 °C. It has thus been theorized that the vapor bubble generated allows fragmentation to take place by conducting the thermal effects of the laser onto the stone. Finally, as further confirmation of the thermal mechanism, breakdown products were found on the surfaces of treated stones that indicated stone surface temperatures >206° at the time of lithotripsy.