Background: Among the largest US metropolitan areas, trends in mortality rates for injection drug users (IDUs) with AIDS vary substantially. Ecosocial, risk environment and dialectical theories suggest many metropolitan areas characteristics that might drive this variation. We assess metropolitan area characteristics associated with decline in mortality rates among IDUs living with AIDS (per 10,000 adult MSA residents) after highly active antiretroviral therapy (HAART) was developed. Methods: This is an ecological cohort study of 86 large US metropolitan areas from 1993-2006. The proportional rate of decline in mortality among IDUs diagnosed with AIDS (as a proportion of adult residents) from 1993-1995 to 2004-2006 was the outcome of interest. This rate of decline was modeled as a function of MSA-level variables suggested by ecosocial, risk environment and dialectical theories. In multiple regression analyses, we used 1993-1995 mortality rates to (partially) control for pre-HAART epidemic history and study how other independent variables affected the outcomes. Results: In multivariable models, pre-HAART to HAART era increases in 'hard drug' arrest rates and higher pre-HAART income inequality were associated with lower relative declines in mortality rates. Pre-HAART per capita health expenditure and drug abuse treatment rates, and pre- to HAART-era increases in HIV counseling and testing rates, were weakly associated with greater decline in AIDS mortality. Conclusions: Mortality among IDUs living with AIDS might be decreased by reducing metropolitan income inequality, increasing public health expenditures, and perhaps increasing drug abuse treatment and HIV testing services. Given prior evidence that drug-related arrest rates are associated with higher HIV prevalence rates among IDUs and do not seem to decrease IDU population prevalence, changes in laws and policing practices to reduce such arrests while still protecting public order should be considered.