The escalating problem of the dissemination of carbapenemase-producing bacteria (CPB) has gained worldwide attention. The prompt diagnosis of CPB and precise identification of carbapenemases are imperative to enable specific antibiotic therapy and control the spread of these bacteria. The present study was designed to assess the performance of five important assays for the detection of carbapenemases. The modified carbapenem inactivation method (mCIM), CARBA-5, GeneXpert Carba-R, BD MAX Check-Points CPO, and GeneFields CPE assays were evaluated with an international collection of 159 bacterial isolates, including 93 CPB and 66 non-CPB isolates. The overall accuracy/sensitivity/specificity for carbapenemase detection were 100% (95% CI, 97.7%-100%)/100% (95% CI, 96.1%-100%)/100% (95% CI, 94.6%-100%) for mCIM, 98.7% (95% CI, 95.5%-99.9%)/97.9% (95% CI, 92.5%-99.7%)/100% (95% CI, 94.6%-100%) for CARBA-5, 96.9% (95% CI, 92.8%-99%)/95.7% (95% CI, 89.4%-98.8%)/98.5% (95% CI, 91.8%-99.9%) for GeneXpert Carba-R, 94.3% (95% CI, 89.5%-97.4%)/90.3% (95% CI, 82.4%-95.5%)/100% (95% CI, 94.6%-100%) for BD MAX Check-Points CPO, and 86.2% (95% CI, 79.8%-91.1%)/77.4% (95% CI, 67.6%-85.5%)/98.5% (95% CI, 91.8%-100%) for GeneFields CPE. Interestingly, mCIM and CARBA-5 assays showed 100% accuracy/sensitivity/specificity for detection of the target genes. Furthermore, all the other assays showed comparable high accuracy (96.9% to 100%), sensitivity (100%), and specificity (96.4% to 100%) for the detection of the target genes. On the basis of these results, a new scheme was proposed for their efficient application. These results confirmed the high sensitivity of the evaluated assays, and the proposed scheme is reliable and improves the overall sensitivity and specificity of the assays.