Intravenous busulfan (IVBu) (Busulfex ESP Pharma) is regularly substituted for oral busulfan as part of the standard busulfan and cyclophosphamide (BuCy) preparative regimen for allogeneic stem cell transplantation (ASCT). Oral busulfan was originally dosed 4 times daily, which led to the current accepted dosing schedule for IVBu. Pharmacokinetics (PK) and busulfan clearance allow for once daily dosing now that IVBu is available. We performed a retrospective review of 36 consecutive patients who received the BuCy preparative regimen with IVBu prior to ASCT. Twenty-one males and 15 females with a median age of 46 years (23–64) were treated for AML (n=15), ALL (n=1), CML (n=8), MDS (n=8), NHL (n=2), and multiple myeloma (n=2). IVBu was dosed 0.8 mg/kg 4 times daily for 16 doses (n=16) or 3.2 mg/kg once daily for 4 doses (n=20) on days -7 to -4, and cyclophosphamide was dosed 60 mg/kg once daily for two doses on days -3 and -2. IVBu was dosed by ideal or adjusted ideal body weight and no PK studies were done. Bone marrow (n=6) or peripheral blood (n=30) stem cells were infused on day 0 from HLA matched siblings (n=26) or unrelated donors (n=9), and one partially matched unrelated donor. Engraftment occurred in 34 patients (pts) (94%). Two pts who failed to engraft had bone marrow grafts with low numbers of total mononuclear cells infused. Regimen related toxicity (RRT) included mild VOD in 2 pts (5%) that self resolved, with one pt receiving IVBu 4 times daily and the other once daily. There was no seizure activity or non-infectious interstitial pneumonitis attributed to RRT in any patient. Other RRT were not significantly different between the patients who received 4 times daily or once daily IVBu. For all patients day 100 mortality was 17%, and at a median follow up of 12 months (1–54) 17 pts (47%) survive. Five of 16 pts (31%) survive who received 4 times daily IVBu, and 12 of 20 pts (60%) survive who received once daily IVBu. Three patients received once daily IVBu as outpatients and no patients received 4 times daily IVBu as outpatients. Financial review between day -7 to day 0, days 1–30, days 61–90, and day-7 to day 90 revealed patient charges were not significantly different at these time points between the once daily and 4 times daily dosing groups. In conclusion, this small retrospective single institution study revealed IVBu dosed once daily by ideal or adjusted ideal body weight appeared to have similar RRT, engraftment, survival and cost compared to 4 times daily IVBu when used as part of the BuCy preparative regimen for ASCT.