Aim. To present and clinically analyze a case of “injection drug users” infective endocarditis (IE) to increase awareness among general practitioners and cardiologists about this special variant of IE.Materials and methods. Clinical observation of a 39-year-old female patient with long-term heroin and methadone addiction, viral hepatitis C, who was diagnosed with acute primary IE caused by methicillin-sensitive Staphylococcus aureus localized on the tricuspid and mitral valves. Bilateral septic pulmonary embolism and respiratory failure, secondary anemia, thrombocytopenia, nephrotic syndrome due to secondary glomerulonephritis were observed. On the 21st day of treatment, the patient underwent tricuspid valve replacement surgery with a biological prosthesis and multicomponent reconstruction of the mitral valve, the postoperative period was complicated by the development of exudative pericarditis.Results. The clinical picture and the course of a complex case of “injection drug users” IE are discussed. The difficulties of early diagnostics of IE caused by the absence of pathognomonic clinical manifestations of the disease and the variability of the debuts of IE with the prevalence of extracardiac manifestations is highlighted. The principles of antibacterial therapy and indications for surgical treatment are reviewed.Conclusion. Clinical observation draws the attention to the high probability of diagnosing IE in cases of fever in intravenous drug users and demonstrates both the difficulties of treatment and the possibility of a favorable outcome of this serious disease with timely diagnosis, appropriate antibacterial therapy, and early cardiac surgery.