Prosthetic infection following total joint replacement can have catast
rophic results both physically and psychologically for patients, leadi
ng to complete failure of the arthroplasty, possible amputation, prolo
nged hospitalization, and even death. Although with the use of prophyl
actic antibiotics and greatly improved operating room techniques the i
nfection rate has decreased markedly during the years, challenges stil
l remain for better preventive and therapeutic measures. In this revie
w the in vivo experimental methods for studies of prosthetic infection
are discussed, concentrating on (1) the animal models that have been
established and the use of these animal models for studies of pathogen
esis of bacteria, behavior of biofilm, effect of biomaterials on prost
hetic infection rate, and the effect of infection on biomaterial surfa
ces, and (2) how to design and conduct an animal model of orthopedic p
rosthetic infection including animal selection, implant fabrication, b
acterial inoculation, surgical technique, and the methods for evaluati
ng the results.