Background Hematopoietic stem cell transplantation can be curative for children with difficult to treat leukemia. The conditioning regimen utilised is known to influence outcomes. We report outcomes of the conditioning regimen used at the Alberta Children’s Hospital, consisting of busulfan (with pharmacokinetic target of 3750μmol*min/day +/-10%) for 4 days, higher dose (250 mg/m2) fludarabine and 400 centigray of total body irradiation. Procedure This retrospective study involved children receiving transplant for acute lymphoblastic leukemia (ALL). It compared children who fell within the target range for busulfan with those who were either not measured or were measured and fell outside this range. All other treatment factors were identical. Results Twenty-nine children (17 within target) were evaluated. All subjects engrafted neutrophils with a median (IQR) time of 14 days (8-30 days). The cumulative incidence of acute graft versus host disease was 44.8% (95% CI 35.6 – 54.0%), while chronic graft versus host disease was noted in 16.0% (95% CI 8.7% - 23.3%). At two years, the overall survival was 78.1% (95% CI 70.8% - 86.4%) and event free survival was 74.7% (95% CI 66.4% - 83.0%). Cumulative incidence of relapse was 11.3% (95% CI 5.1% - 17.5%). There were no statistically significant differences in between the group that received targeted busulfan compared with the untargeted group. Conclusion The current regimen used in children with ALL results in outcomes comparable to standard treatment with acceptable toxicities and significant reduction in radiation dose. Targeting Busulfan dose in this cohort did not result in improved outcomes.