Background: Though antipsychotics are effective against symptoms of schizophrenia and prevent relapses, their effect on disability has not been studied in a comparative design. Aim: To compare disability of schizophrenia patients receiving continuous antipsychotic treatment with that of those not receiving or receiving irregular treatment in a rural community setting using a naturalistic comparative study design. Patients and Methods: Disability was assessed in 182 schizophrenia patients living in Thirthahalli Taluk of Shimoga District, Karnataka, using Indian Disability Evaluation and Assessment Scale (IDEAS). Fifty patients (27.5%) were receiving regular treatment in the previous 2 years and their disability was assessed for the period when they were on antipsychotics. The remaining 132 patients (72.5%) had off-antipsychotics periods in the previous 2 years and their disability was assessed for the period when they were off-antipsychotics. Results: Patients on antipsychotics had significantly less disability across all domains of disability and in total IDEAS scores. Multivariate regression analysis showed that treatment status predicted disability scores after controlling for the effects of the confounding factors. Different levels of exposure to antipsychotic treatment were associated with different levels of disability. Conclusions: Treatment with antipsychotics is associated with significantly less disability. There is an urgent need to bring schizophrenia patients under the umbrella of treatment.