The spores of Clostridium perfringens can survive and grow in cooked/pasteurized meat, especially during the cooling of large portions. In this study, 600 MPa high pressure thermal processing (HPTP) at 75 °C for the inactivation of C. perfringens spores was compared with 75 °C thermal processing alone. The HPTP enhanced the inactivation of C. perfringens spores in beef slurry, resulting in 2.2 log reductions for HPTP vs. no reductions for thermal processing after 20 min. Then, the HPTP resistance of two C. perfringens spore strains in beef slurry at 600 MPa was compared and modeled, and the effect of temperature investigated. The NZRM 898 and NZRM 2621 exhibited similar resistance, and Weibull modeled well the log spore survivor curves. The spore inactivation increased when HPTP temperature was raised from 38 to 75 °C. The results confirm the advantage of high pressure technology to increase the thermal inactivation of C. perfringens spores in beef slurry.