Atypical antipsychotics can alleviate the severity of tardive dyskinesia, but few studies have monitored their long-term effects. The present study investigated the effect of risperidone on pre-existing severe tardive dyskinesia among 40 patients with chronic schizophrenia over 48 weeks. The total Abnormal Involuntary Movement Scale (AIMS) score decreased in 35 patients (87.5%) and increased in three patients (7.5%). At the end of the 48-week trial, the mean total AIMS score decreased significantly, from 15.7+/-4.7 (baseline) to 10.6+/-4.4 (P<0.001), with a mean risperidone dosage of 3.6+/-1.5 mg/day. Twenty-three patients (57.5%) were responders with an average total AIMS score decrease of 8.0+/-2.7. Multiple logistic regression analysis controlling for age, gender, duration of illness, index hospitalization duration, risperidone dose, anticholinergic concomitant use and dystonia score change revealed that a change in the parkinsonism score was the most significant factor related to responders (odds ratio 3.476, 95% confidence interval 1.173-10.298). A significant improvement observed in tardive dyskinesia was noted at week 8, and this improvement persisted until week 48. The results show that the effect of risperidone on pre-existing tardive dyskinesia may be beneficial.