Little is known about the frequency, severity, and risk factors for disease in drug- and alcohol-dependent persons without primary medical care. Our aims are to assess the burden of medical illness, identify patient and substance dependence characteristics associated with worse physical health, and compare measures of illness burden in this population. This was accomplished through a cross-sectional study among alcohol-, heroin- or cocaine-dependent persons without primary medical care who were admitted to an urban inpatient detoxification unit. The mean age of these patients was 35.7 (SD 7.8) years; 76% were male and 46% were Black. Forty-five percent reported being diagnosed with a chronic illness, and 80% had prior medical hospitalizations. The mean age-adjusted SF-36 Physical Component Summary (PCS) score was lower than the general U.S. population norm (44.1 vs 50.1; p<0.001). In multivariable analysis, female gender (adjusted mean change in PCS score: -3.71 points, p=.002), problem use of hallucinogens (-3.51, p=0.013), heroin (-2.94, p=0.008), other opiates (-3.20, p=.045), living alone (-3.15, p=.023), having medical insurance (-2.26, p=0.014) and older age (-.22 points per year, p=0.001) were associated with worse health. From these data, it seems that alcohol- and drug-dependent persons without primary medical care have a substantial burden of medical illness compared to age- and gender-matched U.S. population controls. While the optimal measure of medical illness burden in this population is unclear, a variety of health measures document this medical illness burden in addicted persons.