The nail plate forms a barrier that limits the effectiveness of drug delivery in the treatment of nail diseases and prevents the outflow of fluid in the case of subungual hematoma formation. Microperforation of the nail plate through laser radiation can increase the effectiveness of drug delivery and ensure the possibility of blood outflow. This study detected and identified the type and threshold of effects that arise from exposing the nail plate to Yb,Er: Glass (λ = 1.54 μm) and Er:YLF (λ = 2.81 μm) laser radiation. The rate and efficiency of nail plate ablation by the radiation of these lasers were studied. The effect of the storage time of a freshly extracted nail plate in open air on its ablation rate by Er:YLF (λ = 2.81 μm) laser radiation was also investigated. The impact of the Yb,Er:Glass and Er:YLF laser pulses on the nail plate caused bleaching, carbonization, ablation with microcrater formation, and microperforation. The laser energy densities WE (thresholds) required for these effects were determined. The maximum ablation rate for Yb,Er:Glass laser radiation was 8 μm/pulse at W_E= 91±2 J/cm₂, whereas that for Er:YLF laser radiation was 12 μm/ pulse at W_E= 10.5±0.5 J/cm₂. The maximum ablation efficiency for Yb,Er:Glass laser radiation was 0.1 μm/mJ at W_E= 10.5±0.5 J/cm₂, whereas that for Er:YLF laser radiation was 4.6 μm/mJ at W_E= 5.3±0.3 J/cm₂. The laser ablation rate depends on the storage time and conditions of the freshly extracted nail plate. For example, when exposed to Er:YLF laser radiation, the laser ablation rate decreased by half from the initial maximum value in 96 h of air storage and returned to the initial value after 1 h of storage in distilled water.