The objective of this analysis was to assess the mortality rate and risk factors in adults, with substance dependence, who are not receiving primary medical care (PC). Date and cause of death were identified using the National Death Index data and death certificates for 470 adults without PC over a period of almost 4 years after detailed clinical assessment after detoxification. Factors associated with risk of mortality were determined using stepwise Cox proportional hazards models. Subjects were 76% male, 47% homeless, and 47% with chronic medical illness; 40% reported alcohol, 27% heroin, and 33% cocaine as substance of choice. Median age was 35. During a period of up to 4 years, 27 (6%) subjects died. Median age at death was 39. Causes included: poisoning by any substance (40.9% of deaths), trauma (13%), cardiovascular disease (13.6%), and exposure to cold (9.1%). The age adjusted mortality rate was 4.4 times that of the general population in the same city. Among these individuals without PC in a detoxification unit, risk factors associated with death were the following: drug of choice [heroin: hazard ratio (HR) 6.9 (95% confidence interval (CI) 1.6–31.1]; alcohol: HR 3.7 (95% CI 0.79–16.9) compared to cocaine); past suicide attempt (HR 2.1, 95% CI 0.96–4.5); persistent homelessness (HR 2.4, 95% CI 1.1–5.3); and history of any chronic medical illness (HR 2.1, 95% CI 0.93–4.7). Receipt of primary care was not significantly associated with death (HR 0.85, 95% CI 0.34–2.1). Risk of mortality is high in patients with addictions and risk factors identifiable when these patients seek help from the health care system (i.e., for detoxification) may help identify those at highest risk for whom interventions could be targeted. (Authors)