BACKGROUND: Injection site infections among injecting drug users (IDUs) have been associated with serious morbidity and health service costs in North America. This study explores the frequency, factors and costs associated with injection site infections among IDUs in England. METHODS: Unlinked-anonymous survey during 2003/05 recruiting IDUs from community settings at seven locations across England. Self-reported injecting practice, symptoms of injection site infections (abscess or open wound) and health service utilisation data were collected using a questionnaire, participants also provided dried blood spot samples (tested for markers blood borne virus infections). Cost estimates were obtained by combining questionnaire data with information from national databases and the scientific literature. RESULTS: 36% of the 1,058 participants reported an injection site infection in the last year. Those reporting an injection site infection were more likely to be female and aged over 24, and to have: injected into legs, groin, and hands in last year; injected on 14 or more days during the last four weeks; cleaned needles/syringes for reuse; injected crack-cocaine; antibodies to hepatitis C; and previously received prescribed substitute drug. Two-thirds of those with an injection site infection reported seeking medical advice; half attended an emergency department and three-quarters of these reported hospital admission. Simple conservative estimates of associated healthcare costs range from pound 15.5 million per year to as high as pound 30 million; though if less conservative unit costs assumptions are made the total may be much higher (pound 47 million). The vast majority of these costs are due to hospital admissions and the uncertainty is due to little data on length of hospital stays. CONCLUSION: Symptoms of injection site infections are common among IDUs in England. The potential costs to the health service are substantial, but these costs need more accurate determination. Better-targeted interventions to support safer injection need to be developed and evaluated. The validity of self-reported symptoms, and the relationship between symptoms, infection severity, and health seeking behaviour require further research.