Objective To investigate the effect of atypical antipsychotic medicine risperidone on sensory gating P50 deficit in patients with schizophrenia. Methods Twenty-six patients with first-episode schizophrenia and 25 patients with chronic schizophrenia were enrolled in the study. All patients were treated with risperidone of different doses (2 to 6 mg/d). All patients fulfilled the evaluation of sensory gating P50 with the conditioning (S1)-testing (S2) paradigm before treatment and 4 to 6 weeks after treatment. The psychotic symptoms were assessed with Positive and Negative Syndrome Scale (PANSS), and the therapeutic effects were evaluated with PANSS reduction rate. Results There was no significant difference in P50 parameters between the two groups before treatment (P>0.05), and there was no significant correlation between P50 inhibition parameters and disease course, psychotic episodes and psychiatric symptoms (PANSS total score, positive symptoms score, negative symptoms score and general psychopathology symptoms score) of schizophrenia (P>0.05). Except the group main effect for S2 amplitude (P=0.02), there was no significant change for main effect and interaction of the other P50 parameters after treatment (P>0.05). The effect of risperidone on P50 parameters was not related to the therapeutic effect. Conclusion Deficit in sensory gating inhibition exists in both first-episode schizophrenia and chronic schizophrenia, and risperidone in not effective in treating the deficit in sensory gating inhibition of schizophrenia.