Objective To evaluate the cost-effectiveness of blinatumomab (Blincyto) versus standard of care (SOC) chemotherapy in adults with relapsed or refractory (R/R) Philadelphia-chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL) based on the results of the phase 3 TOWER study from a US healthcare payer perspective. Methods The Blincyto Global Economic Model (B-GEM), a partitioned survival model, was used to estimate the incremental cost-effectiveness ratio (ICER) of blinatumomab versus SOC. Response rates, event free survival (EFS), overall survival (OS), numbers of cycles of blinatumomab and SOC, and transplant rates were estimated from TOWER. EFS and OS were estimated by fitting parametric survival distributions to failure-time data from TOWER. Utility values were based on EORTC-8D derived from EORTC QLQ-C30 assessments in TOWER. A 50-year lifetime horizon and US payer perspective were employed. Costs and outcomes were discounted at 3% per year. Results The B-GEM projected blinatumomab to yield 1.92 additional life years and 1.64 additional quality-adjusted life years (QALYs) compared with SOC at an incremental cost of $180,642. The ICER for blinatumomab versus SOC was estimated to be $110,108/QALY gained in the base case. Cost effectiveness was sensitive to the number and cost of inpatient days for administration of blinatumomab and SOC, and was more favorable in the subgroup of patients who had received no prior salvage therapy. At an ICER threshold of $150,000/QALY gained, the probability that blinatumomab is cost effective was estimated to be 74%. Limitations The study does not consider the adverse events of the treatment; no adjustments for long-term transplant rates were made. Conclusions Compared with SOC, blinatumomab is a cost-effective treatment option for adults with R/R Ph- B-precursor ALL from the US healthcare perspective at a willingness-to-pay threshold of $150,000 per QALY gained. The value of blinatumomab is derived from its incremental survival and health-related quality of life (HRQL) benefit over SOC