The comorbidity of schizophrenia/schizoaffective disorder and substance use is a major psychiatric concern that is associated with aggressive and suicidal behavior. This study investigated the clinical correlates and characterizes adolescent psychotic inpatients with and without comorbid substance use. We performed a retrospective study of 188 adolescent inpatients who were admitted between the years 1994 and 2004 to the inpatient unit of Geha Mental Health Center and who were diagnosed as suffering from either schizophrenia or schizoaffective disorder. The substance-using psychotic inpatients were found to have more relatives with substance-related disorders, fewer comorbid anxiety disorders, lower scores on the Brief Psychiatric Rating Scale and Hamilton Scale for Depression, higher scores on the Overt Aggression Scale, and they were more suicidal than the nonsubstance using inpatients. Adolescent inpatients with schizophrenia and schizoaffective who use substances possess differential clinical characteristics and particular correlates that justify adopting a specific approach to this high-risk clinical subgroup.