Introduction: Intravenous drug use is an increasing social challenge and a predisposing condition to infective ENDOCARDITIS. Data on infective ENDOCARDITIS in intravenous drug users in our society are limited. The aim of this study is determining the clinical features, site of involvement and bacteriologic findings of infective ENDOCARDITIS in intravenous drug users.Materials and Methods: In this descriptive study, injection drug users who admitted at Infectious Diseases Ward, Imam Reza Hospital in a 5 years period (2001-2005), were reviewed and patients characteristics, the results of blood cultures, echocardiographic study, chest imaging and other standard blood testing were collected in questionnaires. Statistical analysis of data was done by SPSS-11 software.Results: A total of 38 cases of infective ENDOCARDITIS occurred in 34 patients. All of these patients were men with a mean (+/- SD) age of 30.4 +/- 7.1 years. The tricuspid valve was involved in 26 cases (74.3%), the mitral valve in 4 cases (11.4%), the mitral and tricuspid valve in 4 cases (11.4%), and the mitral and aortic valve in 1 case (2.9%). The blood cultures were negative in 28.9% 0f cases; microorganisms identified in positive blood cultures included Staphylococcus aureus (77.8%, MRSA in 33.3% and MSSA in 44.4% of cases), Enterococcus (7.4%), Streptococcus pyogenes (7.4%) and Klebsiella pneumoniae (7.4%). Eight patients (21.1%) underwent surgery, and nine (23.7%) of patients died.Conclusion: Infective ENDOCARDITIS in intravenous drug users affects the right side of the heart more commonly. Staphylococcus aureus is still the most frequent organism isolated from blood cultures, but the frequency of methicillin resistant staphylococci, organisms with higher resistance to medical therapy, is increasing. Thus, the suggested empirical regimen for the treatment of infectious ENDOCARDITIS is a combination of cloxacillin, gentamycin and vancomycin. This regimen would be changed on the basis of the results of the blood culture and the pattern of antibiotic susceptibility.