This study aimed to evaluate the cost-effectiveness of autologous stem cell transplant plus CAR-T (ASCT + CAR-T) therapy compared to CAR-T therapy among relapsed/refractory large B-cell lymphoma (r/r LBCL) patients based on real-world data.Complete response rate (CR), adverse events (AE), and total treatment cost were identified and compared between the two therapy groups. Using a decision analytic model based on standard clinical flow, incremental cost-effectiveness ratios (ICERs) for overall survival were calculated with stratification by disease stage and hormone-receptor status. A total of 76 patients received CAR-T therapy and 81 underwent ASCT + CAR-T therapy. The average total treatment cost was ¥242,265.44 for the CAR-T group and ¥321,649.84 for the ASCT + CAR-T group (p < 0.001), 44.70% and 58.02% patients achieved CR at 6-month respectively (p = 0.1). Grade III or higher cytokine release syndrome events occurred in 6.8% of the CAR-T group and 13.6% of the ASCT + CAR-T group (p < 0.001). The ICER was ¥5,974.21 per 1% CR rate increase. The use of ASCT + CAR-T for r/r LBCL patients may lead to better effectiveness but also higher treatment costs. Commercial CAR-T demonstrated a higher CR rate but higher treatment costs compared to in-hospital CAR-T formulations. Our research provides support for the cost-effectiveness of different treatment option for r/r LBCL patients.