Background: BuCy is considered a standard myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT). However its use is limited by significant regimen related toxicity. Several reports suggest that the combination of busulfan and fludarabine(BuFlu) in ablative doses may provide effective control of myeloid neoplasms with less toxicity. This study evaluated the effect of replacing BuCy with BuFlu for myeloablative conditioning in myeloid neoplasms. Methods: Retrospective analysis of patients (pts) with myeloid neoplasms who underwent allogeneic HSCT after myeloablative conditioning regimen with BuFlu or BuCy between 2006 and 2012 was done. Forty five pts received BuFlu and 38 BuCy. Ten (22.2%) pts in BuFlu and 3 (8%) pts with BuCy had an HLA mismatched transplant. Median age was 58 (range 22-68) in BuFlu group and 53 (range 19-68) in BuCy. Disease risk by CIBMTR classification was advanced in 27 (60%) pts in BuFlu group and 10 (26.3%) in the BuCy. HSCT Comorbidity Index score was high in 24 (53.3%) pts in BuFlu and 17(44.7%) in BuCy. GVHD prophylaxis consisted of tacrolimus and methotrexate in all pts in BuFlu and in 81.6 % pts in BuCy with 7 pts receiving cyclosporine and mycophenolate. Thymoglobulin was administered in unrelated and mismatched donor grafts. Cox proportional hazard models were used to obtain the hazard ratios and 95% confidence intervals. Results: All pts engrafted except 1 in the BuCy group. Mortality at day 100 post-transplant was 4.4% in BuFlu and 21% in BuCy (p=0.038). Grade 3 and 4 GVHD was diagnosed in 6.6% in BuFlu and 21% in BuCy group. Risk of relapse or death for pts in the BuCy group was 2.17 times (95% CI 1.08-4.355, p=0.028) higher than for pts in the BuFlu group with a median follow up of 554 days. The trend for overall survival(OS) was better in BuFlu group compared to BuCy (HR 1.97, 95% CI 0.97-3.97, p=0.059). Relapse free survival was also favored in BuFlu pts compared to BuCy (HR 1.550, 95% CI 0.607-3.960, p=0.359) Conclusions: In our experience we found that conditioning with BuFlu is better tolerated, has better 100 day mortality, improved time to progression and OS, in spite of the fact that the pts in BuCy group had a higher CIBMTR disease risk score.