OBJECTIVE： To establish the method for simultaneous determination of risperidone （RIS） and 9-hydroxyrisperidone （9-OH-RIS） in human plasma. METHODS： After liquid-liquid extraction of plasma sample， using AF2672 as internal standard （IS）， LC-MS/MS was adopted. The determination was performed on XtimateTM C18 column with mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate solution （containing 0.1％ formic acid）（37 ∶ 63，V/V，pH＝3.2） at the flow rate of 0.25 mL/min. The column temperature was 40 ℃， and the sample size was 6 μL. The ESI was equipped and quantitative analysis was operated in positive ion and MRM mode. The mass transition ion-pairs were followed as m/z 411.26→191.02 for RIS， m/z 427.21→206.91 for 9-OH-RIS and m/z 418.00→175.95 for IS. RESULTS： The linear range of RIS was 0.2-50.0 ng/mL （r＝0.999 7） and 9-OH-RIS was 1.0-200.0 ng/mL （r＝0.998 7）. RSDs of inter-day and intra-day were all lower than 15％， and the method recoveries were 92.42％-104.81％ and 94.51％-100.57％； matrix effects were 98.33％-107.09％ and 91.05％-105.80％； extraction recoveries were 78.11％-92.62％ and 76.32％-85.09％， respectively. The plasma concentrations of RIS and 9-OH-RIS in 78 schizophrenic patients were （13.58±8.31） and （25.62±15.52） ng/mL. CONCLUSIONS： The developed method is simple， sensitive and specific， which is suitable for routine drug monitoring and acute toxic analysis in patients receiving risperidone.