Infective endocarditis has been associated with underlying cardiac pathology and streptococci infections. Intravenous drug use (IVDU) is increasingly implicated as a contributing factor, resulting in a shift to a younger patient demographic, tricuspid valve involvement, severe staphylococcal infection, and unique management challenges. The objective of this study was to describe the clinical features, management and outcomes of patients with IVDU-associated infective endocarditis in the Australian context. A retrospective review of all episodes of IVDU-associated infective endocarditis at a tertiary hospital in Melbourne, Australia, from 2008 to 2015, was conducted. Included cases met Duke Criteria for 'definite' or 'possible' infective endocarditis, and had a history of IVDU within 3 months of presentation. Demographic data, substance use history, clinical features, surgical intervention, follow-up, and mortality data was collected. We explored factors associated with surgical intervention, recurrence and mortality. Fifty-five (55) episodes of IVDU-associated infective endocarditis were identified in 46 patients; the median age was 40 years and 58% were male. The tricuspid valve was most commonly affected (38%), and left heart pathology was documented in 53% of cases. Methicillin-sensitive Staphylococcus aureus was the most common pathogen (67%). Thirty-six (36%) per cent of patients underwent surgical intervention, and all patients received antibiotics as a component of treatment, with a median duration of 42 days (IQR 21, 42 days). Heart failure and a vegetation larger than 1 cm were significantly associated with surgical intervention. Total mortality was 14.5%; surgical mortality was 10%. Opioid replacement therapy and the absence of psychiatric co-morbidities were protective factors for surgical intervention and disease recurrence. In contrast to common perception, left-sided endocarditis was more common than tricuspid valve endocarditis. Left heart pathology is typically a more severe clinical entity, however, our study determined mortality rates remained similar when compared to right heart pathology. Further research is required to assess rates of left sided disease in the IVDU population, and elucidate the relationship between IVDU and left heart pathology.