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Context: Schizophrenia is mostly treated with atypical antipsycotics, which may be required for lifetime. Olanzapine is commonly used in this condition, whereas levosulpiride is approved in India for the same. Knowing the effect of these drugs on psychomotor function helps in choosing a suitable drug to a particular patient based on his daily activities. Aims: The aim is to compare the effect of levosulpiride and olanzapine on psychomotor performance, efficacy, and adherence in patients with schizophrenia. Settings and Design: This was open-label, parallel arm, prospective observational study carried out in a tertiary care hospital of central India from December 2019 to December 2021. Subjects and Methods: Thirty-six patients visiting psychiatry OPD, diagnosed by treating psychiatrist as schizophrenia were assessed by CFFT, hand steadiness test (HST), arithmetic ability test, and reaction time (RT) for psychomotor function, and symptoms were scored on positive and negative syndrome scale (PANSS) and brief negative symptom scale (BNSS) rating scales at the first visit, end of 4 and 8 weeks. Adherence was assessed by the Medication adherence rating scale at 8 weeks. Results: Statistically significant increase in RT was seen in both levosulpiride (P = 0.04) and olanzapine (P = 0.0065) groups, whereas only the olanzapine group had a significant change in CFFT (P = 0.04) and HST (P = 0.01) at 8 weeks. On head-to-head comparison, a statistically significant worsening in HST score (P = 0.01) was seen in olanzapine group. Both the groups had significant decreases in all PANSS (P < 0.001) and BNSS (P < 0.001) scores. When change in PANSS and BNSS scores were compared with each other, the levosulpiride group had a significantly more decrease in scores on PANSS negative scale (P = 0.03). Patients in both groups were adherent to treatment. Conclusions: Our study concluded that levosulpiride is better than olanzapine on its fine motor control. Both the drugs increase RT while only olanzapine worsened fine motor control and CFF. Both the drugs were effective for schizophrenia with 8 weeks treatment, while levosulpiride is superior to olanzapine in improving negative symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]