Abstract: OBJECTIVE To investigate whether DRD2, ANKK1 and 5-HTR2A genetic polymorphisms could influence acute extrapyramidal symptoms induced by risperidone. METHODS A total of 101 schizophrenic patients, treated with risperidone alone at the dose of 4-6 mg for 4 weeks, were recruited. Treatment Emergent Symptom Scale (TESS) was used to evaluate extrapyramidal symptoms. The score ≥ 2 in any dimension of dystonia, tremor, akathisia or torsion dystonia was regarded as the occurrence of acute extrapyramidal symptoms. iMLDR (improved multiple ligase detection reaction) was performed to detect the genetic polymorphisms of DRD2(rs1799978, rs6275), ANKK1(rs1800497) and 5-HTR2A(rs6311, rs7997012). Chi-square test and multivariate logistic stepwise regression analysis were run to estimate the effects of DRD2, ANKK1, 5-HTR2A genetic polymorphisms on acute extrapyramidal symptoms induced by risperidone. RESULTS Chi-square test showed that rs7997012 significantly influenced the occurrence of acute extrapyramidal system(χ²=4.98, P=0.026). Logistic analysis demonstrated that rs1800497(P=0.038, OR=0.327, 95%CI:0.144-0.938) and rs7997012(P=0.050, OR=0.410, 95%CI:0.168-1.002) genetic polymorphisms had a statistical significance on the occurrence of acute extrapyramidal reaction in an interaction manner. Our present study did not find any correlation of rs1799978, rs6275, rs6311 with acute extrapyramidal reaction of risperidone. CONCLUSION The ANKK1 and 5-HTR2A genetic polymorphisms maybe associated with the occurrence of acute extrapyramidal symptoms induced by risperidone. And this association may differ from the different combinations of their genotypes.