The purpose of the current study was to assess the rate of substance use in patients with medical diseases who were admitted to different wards at Shiraz hospitals affiliated to the Shiraz University of Medical Sciences. Data were gathered from 600 randomly selected patients by a structured interview that included DSM-IV criteria for substance dependency. The mean ages for men and women were 45.8 and 44.7 years, respectively. In this group, 76.7% of the men and 83.7% of the women were married. The majority (29%) of the patients were current nicotine users, and 7.2% were opium users; none used cocaine or LSD. The reported reasons for initial use of substance(s), in order of frequencies, were enjoyment, modeling and release of tension; for current users the reasons were habit, enjoyment and need. Substance use, especially cigarettes, was found to be common among patients. Cultural attitudes toward substance use were thought to affect the type and amount of use. These findings can be considered when planning preventive programs.