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Aripiprazole is a second-generation antipsychotics, acting as a partial dopamine D2 receptor agonist. Previous studies on aripiprazole for tardive dyskinesia (TD) treatment were limited and inconclusive. This study was aimed to examine the effectiveness of aripiprazole in psychotic patients with a pre-existing TD. This was an open-label 24-week prospective cohort study conducted in a public mental hospital in Northern Taiwan from January 2009 to February 2010. Psychotic patients were cross-titrated of prior antipsychotics with aripiprazole, and the severity of TD was assessed at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24. The primary study outcome was the change of TD severity, assessed by Abnormal Involuntary Movement Scale (AIMS) total score. Responder was defined as the reduction of AIMS total scores of no less than 50% from baseline to the study endpoint (24 weeks). Thirty psychotic patients with neuroleptic-induced TD were recruited. The AIMS total scores significantly decreased from baseline to the study endpoint (−7.17±5.55). The significant decrease of AIMS total scores started at week 2 (P<0.0001), and the change remained significant throughout the entire study period (P<0.0001). A greater severity of TD (adjusted odds ratio: 1.35, 95% confidence interval: 1.04–1.76, P=0.03) or a lower severity of parkinsonism (adjusted odds ratio: 0.78, 95% confidence interval: 0.61–0.99, P=0.04) at baseline was significantly associated with treatment responders. Our findings implicated that aripiprazole can be a promising treatment for clinicians considering drug switch in psychotic patients with TD. Further large randomized, controlled trials are warranted to confirm our findings.