Laser skin perforation is an effective and promising technique for use in blood collection. In this study, the relation between the perforation profile of skin and laser irradiation at various energies is discussed. Increasing laser energy does not uniformly expand the size and depth of a hole because the shallow depth of field (DOF) of the focused light primarily concentrates energy on the skin surface. In practice, the hole gradually transforms from a semielliptical shape to an upside-down avocado shape as the laser energy increases. This phenomenon can increase the amount of bleeding and reduce pain. The findings support the feasibility of developing an accurate laser skin perforation method.