OBJECTIVES: The optimal intensity of conditioning prior to allogeneic hematopoietic stem cell transplants (HSCT) remains uncertain. We present the result of the prospective socio-economic evaluation associated with a randomized study comparing two levels of intensity reduction. METHODS: We compare reduced intensity conditioning regimen (RIC= Fludarabine, oral myleran and anti-thymocyte-globulin) and non myeloablative conditioning regimen (NMAC= Fludarabine and total body irradiation). Direct medical transplant costs were estimated by micro-costing on the basis of patients’ CRF until 18 months after transplant. Costs of treatment of progression were estimated within five years after transplant. Cost-effectiveness analysis was performed using overall survival (OS) and disease free survival (DFS) as endpoint. Health-related quality of life (HRQL) was measured prospectively by the EORTC QLQ-C30 questionnaire administered seven days before transplant and on days +30 +80 +180 and +360. Linear mixed model analysis was performed to test whether there were differences in HRQL outcomes within and between the two groups over time. GVHD occurrence was included in the model. RESULTS: A total of 139 patients with hematological malignancies were treated (RIC: N=69; NMAC: N=70). Survival and DFS at one and five years were identical after RIC and NMAC. The mean total cost per patient was not different between groups (83,656€ for RIC vs. 72,592€ for NMAC, NS). This is related to decreased post graft costs for NMAC (-22,815€, p=0.002) being offset by increased costs of disease progression (+11,750€, p=0.008). Using DFS as endpoint, the RIC is cost-effective: incremental cost-effectiveness ratio=978.64 [95%IC=313.23-2447.91]. Using OS no differences were found between the two groups. RIC had a stronger negative impact on patients' HRQL independently of GVHD. CONCLUSIONS: The results confirmed the relapse/toxicity arbitrage associated with the choice of the allo-HSCT conditioning regimen. Moreover, the importance of the choice of endpoints and follow-up times in the economic evaluation of cancer treatment is highlighted.