The aims of this study were to assess the factor structure, validity, and reliability of the Persian translation of the Toronto Alexithymia Scale-20 (TAS-20) and to examine different models of the TAS-20 in Iranian patients with various psychiatric disorders. Participants were 839 patients with psychiatric disorders, including obsessive-compulsive disorder (OCD) (n = 80), schizophrenia (n = 82), bipolar disorder (BD) (n = 100), alcohol dependence (n = 81), major depressive disorder (MDD) (n = 95), psychosomatic disorders (n = 92), anxiety disorders (n = 85), post-traumatic stress disorder (PTSD) (n = 90), attention deficit hyperactivity disorder (ADHD) (n = 55), and suicide attempts (n = 79). Results indicated that the three-factor TAS-16 fit the data well, after removing four items from the externally-oriented thinking (EOT) subscale. In addition, the total score and subscales had strong internal consistency and concurrent validity. An alternative three-factor model and a four-factor model, which both allow the reverse-coded EOT items to load on a separate factor, also had an acceptable fit. The results suggest that after deleting four items from the EOT subscale, the 16-item TAS is a reliable scale among Iranian psychiatric patients. Moreover, the alternative three-factor and four-factor structures may be appropriate to apply among Iranian patients.