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Background Standard of care (SoC) for transfusion-dependent β-thalassemia (TDT) requires lifelong, regular blood transfusions as well as chelation to reduce iron accumulation. Objective This study investigates the cost-effectiveness of betibeglogene autotemcel ('beti-cel'; LentiGlobin for β-thalassemia) one-time, gene addition therapy compared to lifelong SoC for TDT. Study design Microsimulation model simulated the lifetime course of TDT based on a causal sequence in which transfusion requirements determine tissue iron levels, which in t