ABSTRACT Disk diffusion testing is widely used to detect methicillin resistance in staphylococci, and cefoxitin is currently considered the best marker for mecA -mediated methicillin resistance. In low-inoculum diffusion testing (colony suspension at 10 ⁶ CFU/ml), the addition of moxalactam in combination with cefoxitin has been reported to improve on cefoxitin alone for the detection of methicillin-heteroresistant staphylococci. However, moxalactam is absent from EUCAST and CLSI guidelines, which use high-inoculum diffusion testing (colony suspension at 10 ⁸ CFU/ml), calling into question the potential interest of including moxalactam in their recommendations. The inhibition zone diameters of cefoxitin and moxalactam, alone and in combination, were evaluated for concordance with mecA and mecC positivity in a large collection of clinical Staphylococcus isolates (611 Staphylococcus aureus , Staphylococcus lugdunensis , and Staphylococcus saprophyticus isolates and 307 coagulase-negative staphylococci other than S. lugdunensis and S. saprophyticus isolates, of which 22% and 53% were mecA -positive, respectively) and in 25 mecC -positive S. aureus isolates using high-inoculum diffusion testing. Receiver operating characteristic, sensitivity, and specificity analyses indicated that the detection of mecA - and mecC -positive and negative isolates did not improve with moxalactam, either alone or in combination with cefoxitin, compared to cefoxitin alone. These findings were similar in both the S. aureus / S. lugdunensis / S. saprophyticus group and in the coagulase-negative staphylococci group. Our results do not support the use of moxalactam as an additional marker of methicillin resistance when testing with high-inoculum disk diffusion.