Methamphetamine is an illicit psychostimulant that can produce psychotic symptoms similar to those seen in a primary psychotic disorder such as schizophrenia. During an acute episode, the symptoms of methamphetamine-associated psychosis (MAP) can be difficult to distinguish from those of schizophrenia, making a correct diagnosis difficult. This distinction is crucial to understanding the cause of the illness, but very few studies have been conducted to assess these differences. The aim of this study was to determine the differences between the demographic and clinical characteristics and psychopathology of patients diagnosed with methamphetamine-associated psychosis and schizophrenia. A comparative cross-sectional study was conducted with a total of 201 patients who had acute psychosis and were admitted to the psychiatric ward of a general hospital in the Klang Valley. 94 patients were diagnosed with methamphetamine-associated psychosis and 107 with schizophrenia. Significant differences were found in some domains. Multiple logistic regression revealed that patients with methamphetamine-associated psychosis were more likely to be in a younger age group (odds ratio, OR =0.89, 95% confidence interval, CI: 0.80-0.99), have a family history of drug dependence (OR =16.91, 95% CI: 1.02-279.06), have no family history of mental illness (OR =0.04, 95% CI: 0.00-0.55), with a shorter length of stay on the ward (less than 1 week) (OR =0.01, 95% CI: 0.00-0.06), were more likely to be physically fixated (OR 0.05, 95% CI: 0.01-0.38), exhibited grandiosity (OR: 1.92, 95% CI: 1.04-3.56) and had a good rapport (OR:0.44, 95% CI: 0.25-0.79). There were demographic, clinical and psychopathological differences between acute psychosis in methamphetamine-associated psychosis and schizophrenia. Identifying the most important predictors can help to make the correct diagnosis and plan the most appropriate treatment for the illness.