This paper investigates heat transfer of blood vessels subject to transient laser irradiation, where the irradiation is extremely short times and has high power. The modified Fourier heat conduction model (Cattaneo–Christov flux) and Heaviside step function are used in describing the thermal relaxation and temperature jump characteristics in initial time. A novel auxiliary function is introduced to avoid three-level discretization and temporal–spatial mixed derivative, and the numerical solutions are obtained by Crank–Nicolson alternating direction implicit (ADI) scheme. Results indicate that the temperature distributions in blood vessels strongly depend on the blood property, the laser exposure time, the blood flowrate (Reynolds number) and the thermal relaxation parameter. The isothermal curve exhibits asymmetric characteristics due to the impact of blood flow, and the higher blood velocity leads to more asymmetric isotherm and less uniform thermal distribution. Further, the heat-flux relaxation phenomenon is also captured, and its effect on blood temperature becomes more noticeable as blood flows downstream of blood vessels.