To estimate mean patient costs of CRS and NE for R/R LBCL population treated in the third-line or later with CAR T-cell therapy (lisocabtagene maraleucel [liso-cel], axicabtagene ciloleucel [axi-cel], and tisagenlecleucel). This economic model estimated 2019 provider costs using CRS and NE rates from clinical trials; CRS and NE management costs were estimated from a liso-cel study (Abramson, ASCO 2019; Yescarta PI; Kymriah PI). Grade 1–2 CRS was 40%, 81%, and 51%; grade 3–4 CRS was 2%, 13%, and 23% with liso-cel, axi-cel, and tisagenlecleucel, respectively (Lee criteria were used for liso-cel and axi-cel; Penn criteria were used for tisagenlecleucel). Grade 1–2 NE was 20%, 56%, and 40%; grade 3–4 NE was 10%, 31%, and 18% with liso-cel, axi-cel, and tisagenlecleucel, respectively. Means and 95% confidence intervals (CI) for types/grades of CRS and NE were estimated using Monte Carlo simulation (1000 runs). Assumptions were made regarding data inputs. Mean (95% CI) per-patient costs for all-grade CRS and NE were $16,347 ($15,988–$17,482), $50,088 ($49,053–$53,570), and $43,334 ($42,403–$46,344) for liso-cel, axi-cel, and tisagenlecleucel, respectively. Mean (95% CI) per-patient costs were $7715 ($7540–$8251), $23,309 ($22,817–$24,928), and $27,550 ($26,974–$29,465) for CRS with liso-cel, axi-cel, and tisagenlecleucel, respectively, and $8632 ($8447–$9231), $26,779 ($26,236–$28,641), and $15,784 ($15,429–$16,879), respectively, for NE. For an institution treating 100 patients with R/R LBCL with a CAR T-cell therapy cost of $373,000, the opportunity gain of using liso-cel could result in the ability to treat an additional 9.0 and 7.2 patients versus axi-cel and tisagenlecleucel, respectively. Potential cost offsets for liso-cel due to lower CRS and NE rates were $33,741 and $26,987, versus axi-cel and tisagenlecleucel, respectively, showing that differences in safety profiles among CAR T-cell therapies are economically important.