Introduction The prevalence of obesity and associated cardiometabolic comorbidity is significantly higher among patients diagnosed with schizophrenia compared to the general population (Mitchell et al. Schizophr Bull 2013;39:306-18) Objectives To evaluate the effect of 12 months of treatment with lurasidone, risperidone, or quetiapine XR (QXR) on weight and body mass index (BMI) in subjects with schizophrenia. Methods A post-hoc, observed case (OC) analysis was performed on pooled data from 6 clinical studies that evaluated the safety of 12 months of treatment with lurasidone (40–120mg/day; n=471), risperidone (n=89), and QXR (n=33). Results The mean weight at baseline in the lurasidone, risperidone and QXR groups was 72.8, 80.8, and 72.4kg; with 18.5%, 32.6%, and 15.2%, respectively, meeting standard BMI criteria for obesity. The mean change in weight (kg) in the lurasidone, risperidone and QXR groups, respectively, was −0.5, +1.7, and +1.5 at 3 months; −0.4, +2.2, and +1.5 at 6 months; and −0.4, +2.6, and +1.2 at 12 months. A clinically significant increase in weight (≥7%) occurred in the lurasidone, risperidone and QXR groups in 15.7%, 25.0%, and 15.2% of subjects, respectively, at 12 months; and a decrease of ≥7% in weight occurred in 18.6%, 6.8%, and 9.1% of subjects, respectively at 12 months. Similar changes in BMI were observed at 12 months. Conclusions The results of this pooled analysis of subjects with schizophrenia who completed 12 months of treatment suggest that lurasidone is associated with a low potential for clinically significant weight gain.