Introduction: In Poland, busulfan conditioning is used for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cost-utility analyses comparing alternative conditioning regimens in patients undergoing allo-HSCT have not been conducted so far. Material and methods: A United Kingdom-based partitioned survival model was adapted to the Polish setting to compare treosulfan to low-dose busulfan conditioning regimen from the public payer’s perspective in Poland. Patient characteristics, overall survival (OS), event-free survival (EFS), and the rate of adverse events were obtained from the randomized MC-FludT.14/L trial. Parametric survival models of up to 5 years (the cure threshold), with subsequent mortality defined using survival of the general population of Poland adjusted for cancer survivors, were used to extrapolate OS and EFS beyond the trial duration. Published utilities were adjusted for age using age-dependent general population utilities. The costs of treatment, adverse events, and inpatient/outpatient care were assessed via official remuneration schemes. Results: Treosulfan-based conditioning outperformed low-dose busulfan, i.e. it was more effective with incremental quality-adjusted life years (QALY) of 0.78 and less expensive by 1,139 PLN per patient over the lifetime horizon. Deterministic sensitivity analyses revealed treosulfan was highly cost-effective (i.e. incremental cost-utility ratio was lower than the gross domestic product per capita in Poland) compared to low-dose busulfan, if most uncertain parameters are changed or alternative scenarios are implemented. The probability of treosulfan being cost-effective with a threshold of 155,514 PLN was 99.6%. Conclusions: Compared to low-dose busulfan, treosulfan is a highly cost-effective conditioning regimen for allo-HSCT patients ineligible for standard conditioning regimens.