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Cylindrical porous tantalum intramedullary implants were inserted in the proximal right tibia of 30 male white rabbits after administration of antibiotic prophylaxis. Four weeks later and without antibiotic prophylaxis, 20 animals received 1 ml of inoculum of two different concentrations (study groups A and B) of CA\u2010MRSA strain through an ipsilatelar femoral artery catheter. The remaining 10 received normal saline instead (control group C). Surviving animals were sacrificed 4 weeks later. Sterile bone, bone marrow biopsies, and implants were harvested for culture and histological evaluation. Ten animals receiving 5\u2009\u00d7\u200910<jats:sup>8<\/jats:sup>cfu\/ml (group A) died within 48\u201372 h due to septic shock. Blood cultures were positive; histology demonstrated acute infection. Ten animals received bacterial load of 3\u2009\u00d7\u200910<jats:sup>8<\/jats:sup>cfu\/ml (group B) and all survived; two had negative Gram\u2010stain and cultures but PCR and RT\u2010PCR results demonstrated the viability of the microorganisms, while periprosthetic osteolysis and histological evaluation indicated subacute osteomyelitis; eight animals established periprosthetic infection, osteomyelitis, and septic arthritis documented by positive Gram\u2010stain, cultures, subperiosteal reaction, and chronic infection on histology. Control group specimens demonstrated no signs of infection. Histopathological semiquantitative scoring was used to compare the three groups. Comparison of groups A and B with control group and between group A and B showed statistically significant difference (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in all parameters except for periosteal reaction between groups B and C (<jats:italic>p<\/jats:italic>\u2009=\u20090.354). This novel, reproducible experimental model will facilitate the study of hematogenous CA\u2010MRSA IRIs. \u00a9 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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