Abstract <p>The results of application of an original antimicrobial polymer hydrogel based on polyvinylpyrrolidone as a local depot of antibacterial drugs for the prevention of chronicization of the infectious process during hip joint prosthetics in implant-associated infection in rabbits are presented. At the first stage, intramedullary osteomyelitis of the femur of the animals was modeled by implantation of the infected limb. On the 14th day, a second surgical intervention with sanitation of the focus of infection, removal of the limb, and unipolar hip arthroplasty was performed. All rabbits were divided into two groups: experimental, with application of the experimental gel at the stage of endoprosthesis (<i>n</i> = 3), and control, without gel (<i>n</i> = 3). After withdrawal from the experiment on the 90th day, a morphological study with evaluation of changes in the soft tissues and medullary canal, as well as microbiological analysis of samples of soft tissues, bone structures, and the removed endoprosthesis stem were carried out. In the control group, <i>Staphylococcus aureus</i> contamination was detected in two out of three animals, while in the experimental group, such bacteria were not detected in any of the samples tested. A comparative analysis of the cellular infiltrate in soft tissues revealed that the amount of multinucleated giant cells was significantly higher in the experimental group, and the amount of neutrophylic granulocytes, as indicators of the activity of the infectious process, were significantly higher in the control group. Thus, the use of the experimental antimicrobial polymeric hydrogel allowed us to prevent the development of a chronic infectious process, despite the fact that endoprosthesis was performed during sanitation of the osteomyelitis focus and a short course of antibacterial therapy. The presence of a pronounced giant cell reaction in soft tissues requires further investigation and at a later time after surgical intervention.</p>