Foamy viral vectors and lentiviral vectors are attractive gene transfer vectors for hematopoietic stem cell gene therapy because they both efficiently transduce stem cells using rapid ex vivo transduction protocols designed to maintain engraftment potential. Here we directly compared the ability of foamy and lentiviral vectors to transduce long-term hematopoietic repopulating cells in the dog model, using a competitive repopulation assay with vectors that express enhanced yellow or green fluorescent proteins (EY/GFP). Mobilized canine peripheral blood CD34(+) cells were divided into two fractions and exposed to either foamy (EGFP) or lentiviral (EYFP) vectors at a multiplicity of infection of 5 in an 18-hr transduction protocol and then reinfused after conditioning with 920 cGy of total body irradiation. Both dogs studied had rapid neutrophil engraftment and multilineage engraftment of transduced cells. Marking was similar for both vectors, particularly at later time points, indicating that both vector types transduce long-term repopulating cells at similar frequencies.