UNLABELLED: Piperacillin-tazobactam (TZP) is a commonly used broad-spectrum agent. OXA-1 β-lactamases drive global Enterobacterales TZP resistance and raise MICs to the clinical breakpoints (8/4-16/4 µg/mL), making susceptibility testing challenging. Two TZP disks are used globally. The first with 100 µg piperacillin and 10 µg tazobactam, established in 1992, is used by laboratories following U.S. FDA and Clinical and Laboratory Standards Institute (CLSI) standards. The second, with 30 µg piperacillin and 6 µg tazobactam, was developed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). When CLSI updated Enterobacterales TZP MIC breakpoints in 2022, it became apparent that the 100/10 µg disk may not accurately predict TZP resistance or susceptibility. In this study, we performed a disk mass titration study using 100 contemporary Enterobacterales isolates, including 40 harboring bla IMPORTANCE: In this article, we address major gaps in contemporary data for piperacillin-tazobactam (TZP) susceptibility testing and evaluate the performance of disk diffusion. TZP is the most common empiric broad-spectrum agent against Gram-negative pathogens and is used as a carbapenem-sparing regimen. OXA-1 β-lactamases drive global Enterobacterales TZP resistance and raise MICs to the clinical breakpoints, making susceptibility testing challenging. In 2022, CLSI revised the Enterobacterales TZP MIC breakpoints. Due to the lack of contemporary correlates, disk diffusion breakpoints were revised using outdated historical data from 1991 and 2003 and yielded unacceptable error rates. Additionally, there is a lack of global consensus on disk potency. The EUCAST TZP disks contain 30 μg piperacillin and 6 μg tazobactam. The CLSI disks, established after TZP approval in 1979 and prior to the widespread prevalence of ESBLs, contain 100 μg piperacillin and 10 μg tazobactam. Here, we evaluate disk diffusion using the 100/10 and 30/6 μg TZP disks with 100 contemporary Enterobacterales isolates, including 40 harboring bla