Objective: The authors carried out an experimental study to evaluate the histological alterations after irradiation of cartilage using Holmium:YAG (Ho:YAG) laser VersaPulse Select 60 watts and Infra Tome Delivery Systems 30° Handpiece (spot size at fiber tip 0.4 mm; Coherent Medical, Palo Alto, CA). Background Data: Recently, some authors reported cases with articular cartilage damage following arthroscopic laser surgery in the knee joint for the treatment of articular cartilage or meniscal pathology. Materials and Methods: The cartilage specimens immersed in saline were exposed to Ho:YAG laser irradiation. The laser wavelength was 2.1 μm, and pulse duration was 250 μsec. Power settings were 0.2-1 joules per pulse and 10-15 Hz. Total laser energy used in these procedures was 1.5 K joules. During the procedures, the handpiece was used at an angle of 30° and at a distance of 1 mm. Results: Electron microscopic evaluation demonstrated that the ultrastructure of the cartilage is preserved in both experiment and control groups. Conclusion: When Ho:YAG laser is used in optimal dosage (optimal joule and Hertz) with optimal technique (keeping the handpiece at an appropriate angle and distance) and avoiding overtreatment, it does not cause cartilage damage.