We analyzed the impact of CD34⁺ cell dose on the outcome of 86 patients undergoing reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation. The RIC was based on fludarabine 150 mg/m² and melphalan 140 mg/m² or busulphan 10 mg/kg. A median of 5.68 × 10⁶ CD34⁺ cells/kg and 2.86 × 10⁸ CD3⁺ cells/kg were infused. All patients receiving more than percentile 75 (p75) of CD34⁺ cells reached complete chimerism in T lymphocytes by days 21 to 28, compared with 44% among those receiving p75 or fewer cells (P = .046). Overall, 30.3% patients developed grade 2 to 4 acute graft-versus-host disease (aGVHD). Among 83 evaluable patients, 55.8% developed chronic GVHD (cGVHD). The dose of CD34⁺ cells infused did influence the development of cGVHD, with a cumulative incidence of extensive cGVHD of 74% vs 47% (P = .02) among patients receiving more than p75 CD34⁺ cells vs those receiving p75 or fewer. Projected overall survival (OS) and event-free survival (EFS) at 43 months were 60% and 46%, respectively. Neither the dose of CD34⁺ cells nor the dose of CD3⁺ cells infused significantly influenced OS and EFS, although among patients categorized as high-risk, 36% of those receiving p75 or fewer CD34⁺ cells relapsed or progressed, compared with only 9% among those receiving more than p75 CD34⁺ cells (P = .07). Among patients receiving p75 or fewer CD34⁺ cells, 36% of high-risk patients relapsed, compared with 10% of low- and intermediate-risk patients (P = .004), while relapse rates were not significantly different between both subgroups when we infused more than p75 CD34⁺ cells, thus indicating that infusing high doses of CD34⁺ cells ameliorates the negative effect of advanced disease status at transplantation. cGVHD was associated with better EFS (63% vs 16% at 43 months for patients with and without cGVHD; P < .0001) and better OS (78% vs 28% for patients with and without cGHVD; P < .001). The number of CD34⁺ cells infused should be tailored to prevent extensive cGVHD among patients categorized as low-risk, while high-risk patients, in whom the graft-versus-leukemia effect may determine disease outcome, should receive high doses of CD34⁺ cells.