Drug injectors are known to have high rates of hospital and emergency room (ER) use. We hypothesized that out-of-treatment injection drug users (IDUs) have higher rates of health service use than methadone-maintained persons, and that heroin injection frequency mediates health service use among drug injectors (IDUs). HIV-negative individuals with a history of drug injection were recruited from a needle exchange program (NEP) and a methadone maintenance treatment program (MMT) in Providence, RI. ER visits, outpatient visits, and hospitalizations in the last 6 months were the dependent variables with number of heroin injections the hypothesized mediator variable. The 472 participants were predominately male (60.6%) and white (82%) with a mean age of 37. NEP clients were more likely than MMT clients to visit an ER (39.2% vs. 29.8%; P=0.03). NEP participants were somewhat more likely to report a hospital admission (16.0% vs. 10.6%; P=0.08). Relative to non-injecting MMT participants, the odds of visiting an ER were 1.80 and 1.67 times higher for subjects recruited through NEP and actively injecting MMT participants, respectively. Additionally, subjects recruited through NEP (OR=2.2) and actively injecting MMT participants (OR=2.3) were over twice as likely to report a hospital admission than non-injecting MMT participants. Each increase of one heroin injection per day increased the expected odds of injection-related infection by a factor of 1.92. NEP clients are more likely to have ER visits and hospitalizations than methadone clients. We describe a pathway by which injection frequency influences health service use.