Background Screening for donor-specific anti-HLA antibodies (DSA) using bead-based multiplex assays to determine transplant suitability is standard practice in many countries. We compared the health benefits and costs of screening preformed DSA using bead-based assay as an add-on test to complement-dependent cytotoxicity (CDC) crossmatch with CDC crossmatch alone, and determined the optimal threshold to determine transplant suitability. Methods Three probabilistic Markov models were developed to compare bead-based assay with CDC and CDC alone. The model assumed a hypothetical cohort of 10,000 patients who received only a single kidney transplant and terminated when all patients were deceased. Results Assuming transplantation was permitted for recipients with no DSA or with a DSA mean fluorescence intensity (MFI) value of 500 or less, screening by bead-based assay and CDC saved 6.5 grafts and U.S. $1,192,303 per 100 transplants compared with CDC alone. If the thresholds were increased to an MFI of 2000 or less and 5000 or less, an extra 6.4 and 6.1 grafts would be saved, with cost savings of U.S. $867,203 and U.S. $830,664 per 100 transplants compared with CDC alone. The total number of kidney transplants performed would have increased by 8 and 9, respectively, but at the expense of an extra 0.1 and 0.4 graft lost per 100 transplants after 5 years. Conclusions Screening using bead-based assay is cost-saving and improves graft outcomes. The greatest benefits and cost-savings are achieved if transplantation occurs at a threshold of MFI of 500 or less or in those without preformed DSA. Increasing the threshold to an MFI of 2000 or less may provide an acceptable balance for improving transplant eligibility without compromising longer-term outcomes.