To better understand residential detoxification use, we assessed the roles of depressive symptoms (DS) and mental health functioning (MHF) on repeat detoxification. A prospective cohort of residential detoxification patients (N=400) without primary medical care was followed over 2 years at 6-month intervals. Subsequent detoxification admissions were examined using a statewide administrative database and DS (Center for Epidemiologic Studies Depression Scale) and MHF (SF-36 mental component summary subscale) measurements at follow-up. Incidence rate ratios of return to detoxification were estimated using multivariable longitudinal Poisson regression. In separate analyses, greater DS and worse MHF predicted higher detoxification use rates. Clinically significant worsening (10 points) of DS and MHF on objective scales predicted a 20% increased rate of detoxification readmission. Male sex, heroin as a problem substance, and race/ethnicity each predicted detoxification use. These data suggest that identifying individuals with DS or worse MHF after detoxification may provide opportunities for clinical intervention to reduce recurrent residential detoxification.