This study used a real-world population as a synthetic comparator for the single-arm TRANSCEND NHL 001 study (TRANSCEND; NCT02631044) to evaluate the efficacy of lisocabtagene maraleucel (liso-cel) compared with conventional (noncellular) therapies in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Inclusion and exclusion criteria for the real-world study closely matched the enrollment criteria in TRANSCEND. The analytic comparator cohort was created by matching and balancing observed baseline characteristics of real-world patients with those in TRANSCEND using propensity score methodology. Efficacy outcomes comparing liso-cel- ( = 257) and conventional therapy-treated ( = 257) patients, respectively, significantly favored liso-cel: overall response rate (74% vs 39%;  < 0.0001), complete response rate (50% vs 24%;  < 0.0001), median overall survival (23.5 vs 6.8 months;  < 0.0001), and median progression-free survival (3.5 vs 2.2 months;  < 0.0001). These results demonstrated a statistically significant and clinically meaningful benefit of liso-cel in patients with third- or later-line R/R LBCL relative to conventional therapies. ClinicalTrials.gov identifier: NCT02631044.