Background: Severe mental illnesses are associated with increased risks for metabolic syndrome (MetS) and other medical disorders, often with unfavorable outcomes. MetS may be more likely with schizoaffective disorder (SzAff) than schizophrenia (Sz). MetS is associated with long-term antipsychotic drug treatment, but relative risk with orally administered vs. long-acting injected (LAI) antipsychotics is uncertain. Methods: Subjects (n = 151 with a DSM-IV-TR chronic psychotic disorder: 89 Sz, 62 SzAff), treated with oral or LAI antipsychotics were compared for risk of MetS, initially with bivariate comparisons and then by multivariate regression modeling. Results: Aside from measures on which diagnosis of MetS is based, factors preliminarily associated with MetS included antipsychotic drug dose, "high-risk" antipsychotics associated with weight-gain, older age and female sex. Defining factors associated with diagnosis of MetS ranked in multivariate regression as: higher fasting glucose, lower LDL cholesterol, higher diastolic blood pressure, and higher BMI. Risk of MetS with antipsychotics ranked: quetiapine ≥ clozapine ≥ paliperidone ≥ olanzapine ≥ risperidone ≥ haloperidol ≥ aripiprazole. Other associated risk factors in multivariate modeling ranked: higher antipsychotic dose, older age, and SzAff diagnosis, but not oral vs. LAI antipsychotics Conclusions: SzAff diagnosis and higher antipsychotic doses were associated with MetS, whereas orally vs. injected antipsychotics did not differ in risk of MetS.