The purpose of this multicenter study was to compare the long-term impact of a preparative regimen with either BUBU or TBI on health status and quality of life (QoL) in childhood acute leukemia survivors treated with hematopoietic SCT (HSCT). Two-hundred and forty patients were included. Sixty-six had received BU, while 174 had received TBI. Median follow-up from HSCT was 10.1 years. Multivariate analyses were performed to assess the occurrence of late effects according to treatment. QoL was assessed in 130 adults using SF-36 questionnaires. Patients developed fewer late complications after BU (2.35 vs 3.01, P=0.03) while the risk to present with at least one complication was equivalent in both groups (87.9% after BU and 93.1% after TBI, P=0.66). Detailed multivariate analyses revealed a lower risk of height growth failure (OR=0.2), cataract (OR=0.1) and iron overload (OR=0.2) after BU, and an increased risk of overweight (OR=3.9) and alopecia (OR=11.2). SF-36 mental and physical composite scores were similar in both treatment groups and proved significantly lower than French norms. Late effects induced by BU might differ from those experienced after TBI. Although less frequent, they are still of considerable importance and may affect patients' QoL.