Abstract: The current study aimed to develop an inactivation strategy for Clostridium perfringens spores in meat through a combination of spore activation at low pressure (100–200MPa, 7min) and elevated temperature (80°C, 10min); spore germination at high temperatures (55, 60 or 65°C); and inactivation of germinated spores with elevated temperatures (80 and 90°C, 10 and 20min) and high pressure (586MPa, at 23 and 73°C, 10min). Low pressures (100–200MPa) were insufficient to efficiently activate C. perfringens spores for germination. However, C. perfringens spores were efficiently activated with elevated temperature (80°C, 10min), and germinated at temperatures lethal for vegetative cells (≥55°C) when incubated for 60min with a mixture of l-asparagine and KCl (AK) in phosphate buffer (pH 7) and in poultry meat. Inactivation of spores (∼4 decimal reduction) in meat by elevated temperatures (80–90°C for 20min) required a long germination period (55°C for 60min). However, similar inactivation level was reached with shorter germination period (55°C for 15min) when spore contaminated-meat was treated with pressure-assisted thermal processing (568MPa, 73°C, 10min). Therefore, the most efficient strategy to inactivate C. perfringens spores in poultry meat containing 50mM AK consisted: (i) a primary heat treatment (80°C, 10min) to pasteurize and denature the meat proteins and to activate C. perfringens spores for germination; (ii) cooling of the product to 55°C in about 20min and further incubation at 55°C for about 15min for spore germination; and (iii) inactivation of germinated spores by pressure-assisted thermal processing (586MPa at 73°C for 10min). Collectively, this study demonstrates the feasibility of an alternative and novel strategy to inactivate C. perfringens spores in meat products formulated with germinants specific for C. perfringens. [Copyright &y& Elsevier]