BACKGROUND:Injection drug use is on the rise in the USA, and skin and soft tissue infections (SSTI) are a common complication, resulting in significant morbidity and mortality. Due to structural barriers to care-seeking, many people who inject drugs avoid formal care and resort to self-care techniques, but little is known about the nature of these techniques, or more generally about the accuracy or breadth of this population's knowledge of SSTIs. METHODS:Semi-structured qualitative interviews were conducted with 12 people who inject heroin in two metropolitan areas: Sacramento and Boston, USA. RESULTS:These interviews reveal a robust and accurate knowledge base regarding skin infections, including the progression from simple cellulitis to an abscess, and acknowledgment of the possibility of serious infections. Nonetheless, there remains a reticence to seek care secondary to past traumatic experiences. A step-wise approach to self-care of SSTI infections was identified, which included themes of whole-body health, topical applications, use of non-prescribed antibiotics, and incision and drainage by non-medical providers. CONCLUSIONS:The reported SSTI self-care strategies demonstrate resilience and ingenuity, but also raise serious concerns about inappropriate antibiotic consumption and complications of invasive surgical procedures performed without proper training, technique, or materials. Harm reduction agencies and health care providers should work to obviate the need for these potentially dangerous practices by improving healthcare access for this population. In the absence of robust solutions to meet the needs of this population, education materials should be developed to optimize the efficacy and minimize the harms of these practices, while empowering and supporting the autonomy of people who use drugs and providing clear guidance on when self-care should be abandoned in favor of formal medical care.