The study determined the prevalence of MetS in patients with schizophrenia at the Psychiatric Unit of the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. This comparative cross-sectional study recruited 348 schizophrenic patients comprising 236 antipsychotic-treated and 112 newly diagnosed treatment-naïve patients. The MetS prevalence was assessed based on World Health Organization (WHO), International Diabetes Federation (IDF), and the National Cholesterol Education Programme, Adult Treatment Panel III (NCEP ATP III) criteria. The overall prevalence of MetS was 14.1%, 20.4%, and 23.6% using NCEP ATP III, WHO, and IDF criteria, respectively, compared to 7.8%, 3.9%, and 2.2% reported in the general Ghanaian population. The prevalence was significantly higher among treated psychiatric patients compared to treatment-naïve group based on NCEP ATP III (17.8% versus 6.2%; p = 0.0001), WHO (26.2% versus 8.0%; p < 0.0001), and IDF (30.3% versus 10.0%; p < 0.0001). MetS was prevalent among patients on atypical antipsychotics compared to typical antipsychotics irrespective of the criteria used (i.e., 17.1% versus 11.1% for NCEP ATP III; 29.5% versus 25.9% for WHO; and 44.3% versus 18.5% for IDF). Using logistic regression model, obesity, raised fasting blood sugar, raised total cholesterol, and decreased high density lipoprotein were observed to be significant predictors of MetS (p<0.05).The study found high prevalence of MetS in Ghanaians with schizophrenia and higher prevalence rate of MetS associated with monotherapy. Regular monitoring of cardiometabolic parameters should be an important therapeutic objective in the management of these patients.