Boning of dry-cured hams involves additional handling which increases the risk of contamination with Listeria monocytogenes. This work studies the ability of E-beam to eliminate this pathogen from boned dry-cured ham (BDH). The destruction kinetics of four L. monocytogenes strains (S2, S4-2, S12-1, and S7-2) and L. innocua NCTC 11288 as a surrogate were determined at doses up to 3 kGy. L. innocua and L. monocytogenes S4-2 were the most radioresistant (D-value = 0.55 kGy). E-beam penetration was studied in blocks extracted from BDH and irradiated with 2–6 kGy. The bilateral treatment of 2 kGy allows the required dose (1.32 kGy) to be absorbed in the innermost part of the block to achieve the food safety objective of “zero tolerance” for this microorganism. This listericidal treatment was also confirmed in whole BDH intentionally contaminated with L. innocua. The sensory analysis of irradiated BDH showed off-odors that were imperceptible after 15 days of storage at 4°C.