ABSTRACT Background and objective: Tramadol misuse is a public health problem in Egypt. The objective of this study was to compare differences between patients with tramadol misuse and patients with heroin use regarding sociodemographic and clinical correlates. Methods: This cross-sectional study included 58 consecutive male patients with heroin use and 37 male patients with tramadol misuse. Patients were assessed by a structural interview of SCID-I of DSM-IV-TR criteria for substance use disorders and comorbid psychiatric disorders. Patients were screened for drugs using a urine test. Results: Patients with tramadol misuse were more likely to be older, to have higher education level, to be married and have a skilled profession than patients with heroin use. Patients with heroin use were more likely to have a higher smoking rate, younger age of onset of smoking, higher family history of substance use disorders, higher incarceration rate than patients with tramadol misuse. Conclusions: Patients with tramadol misuse have more similarities than differences compared to patients with heroin use. Although tramadol has a dual mechanism of action and is seen as a molecule with low misuse potential it should be treated as an opioid use disorder. Q4 Q5 Q2