Background <p>The CD20 × CD3 bispecific antibody glofitamab combined with gemcitabine and oxaliplatin (Glofit-GemOx) has demonstrated clinical efficacy in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL).</p> Aim <p>The aim of this study was to evaluate the cost-effectiveness of Glofit-GemOx versus R-GemOx for relapsed or refractory DLBCL patients following one or more previous lines of therapy from the perspective of healthcare in China.</p> Method <p>A three-state partitioned survival model was constructed based on the STARGLO study to assess the cost-effectiveness of Glofit-GemOx versus rituximab-GemOx (R-GemOx). Quality-adjusted life years (QALYs) were used as health outcomes, and the incremental cost-effectiveness ratio (ICER) was calculated. One-way deterministic sensitivity analyses and probabilistic sensitivity analyses were performed on key parameters to assess the robustness of the base analysis results.</p> Results <p>The costs in Glofit-GemOx regimen were $266,518.83, whereas the costs of R-GemOx regimen were $43,227.09. Compared with the R-GemOx regimen, the Glofit-GemOx regimen resulted in an increase of 0.85 QALYs, yielding an ICER of $262,696.16 per QALY. The ICER significantly exceeded the willingness-to-pay (WTP) threshold of $38,188/QALY and sensitivity analysis revealed the cost of glofitamab had a substantial effect on results.</p> Conclusion <p>Compared with R-GemOx, Glofit-GemOx is not cost-effective compared for relapsed or refractory DLBCL patients in China at current price. A negotiated price reduction for glofitamab could substantially improve its cost-effectiveness profile.</p>