Holmium:YAG lithotripsy of uric acid calculi produces cyanide. The laser and stone parameters required to produce cyanide are poorly defined. In this study, we tested the hypotheses that cyanide production: (1) varies with holmium:YAG power settings; (2) varies among holmium:YAG, pulsed-dye, and alexandrite lasers; and (3) occurs during holmium:YAG lithotripsy of all purine calculi.Holmium:YAG lithotripsy of uric acid calculi was done using various optical fiber diameters (272-940 microm) and pulse energies (0.5-1.5 J) for constant irradiation (0.25 kJ). Fragmentation and cyanide were quantified. Cyanide values were divided by fragmentation values, and fragment sizes were characterized. To test the second hypothesis, uric acid calculi were irradiated with Ho:YAG, pulsed-dye, and alexandrite lasers. Fragmentation and cyanide were measured, and cyanide per fragmentation was calculated. Fragment sizes were characterized. Finally, Ho:YAG lithotripsy (0.25 kJ) of purine and nonpurine calculi was done, and cyanide production was measured.Fragmentation increased as pulse energy increased for the 550- and 940-microm optical fibers (P < 0.05). Cyanide increased as pulse energy increased for all optical fibers (P < 0.002). Cyanide per fragmentation increased as pulse energy increased for the 272-microm optical fiber (P = 0.03). Fragment size increased as pulse energy increased for the 272-microm, 550-microm, and 940-microm optical fibers (P < 0.001). The mean cyanide production from 0.25 kJ of optical energy was Ho:YAG laser 106 microg, pulsed-dye 55 microm, and alexandrite 1 microg (P < 0.001). The mean cyanide normalized for fragmentation (microg/mg) was 1.18, 0.85, and 0.02, respectively (P < 0.001). The mean fragment size was 0.6, 1.1, and 1.9 mm, respectively (P < 0.001). After 0.25 kJ, the mean amount of cyanide produced was monosodium urate stones 85 microg, uric acid 78 microg, xanthine 17 microg, ammonium acid urate 16 microg, calcium phosphate 8 microg, cystine 7 microg, and struvite 4 microg (P < 0.001).Cyanide production varies with Ho:YAG pulse energy. To minimize cyanide and fragment size, Ho:YAG lasertripsy is best done at a pulse energy < or = 1.0 J. Cyanide production from laser lithotripsy of uric acid calculi varies among Ho:YAG, pulsed-dye, and alexandrite lasers and is related to pulse duration. Cyanide is produced by Ho:YAG lasertripsy of all purine calculi.