Despite multiple risk factors for mortality among People Who Inject Drugs (PWID), more research is warranted that examines sub-populations within PWID. Mortality data from PWID participating in longitudinal HIV prevention research in Denver were obtained from The Colorado Department of Public Health and Environment. Risk factors for both all-cause and acute-toxicity related mortality were analyzed using Cox proportional hazards regression. Two-thousand seven individuals were interviewed at baseline. Eighty-six individuals died during the time frame of the study, 58 of which were due to acute-toxicity. Disabled (HR = 3.3, p < 0.001), gay/lesbian-identified (HR = 2.6, p = 0.03), white race/ethnicity (HR = 2.4, p = 0.003), and use of a shared cooker (HR = 2.1, p = 0.01) were important adjusted risk factors. These suggest that drug and HIV interventions should utilize techniques that can address the needs of marginalized populations in addition to HIV drug risk behaviors.