The aim of the study was to investigate the effect of depression on pattern of substance use disorders (SUDs). Consecutive samples of (200) Egyptian male SUD inpatients were examined over 1-year period. Study and control samples were chosen. Study group consisted of 30 patients with comorbid substance dependence and depression. Control group consisted of 30 substance-dependent patients without depression. Semistructured interviews, Addiction Severity Index (ASI) and Hamilton Rating Scale for Depression (HDRS), were applied. Comparison between both groups showed significant differences for prescribed opioid use (100% versus 86%), polysubstance use (73% versus 43%), frequency of suicidal attempts (86% versus 43%), mean of admissions to substance use treatment (SUT) units (5 versus 2.2), mean of abstinence periods (3.8 versus 1.2); study group showed greater medical status impairment (P = .05), social and psychiatric impairment (P = .01). It was concluded that depression might affect SUD as regards type of substance used, pattern of use, suicide rate, duration of hospitalization, rate of rehospitalization, and finally medical, social, and psychiatric status impairment.