The objective of this paper was to assess the effects of switching from typical and/or atypical antipsychotics to ziprasidone, owing to inadequate response or intolerance, in chronic schizophrenic patients. A total of 312 patients were switched to an 8-week, open-label, flexible dose (40-160 mg/day) of ziprasidone. Psychiatric status was evaluated by Positive and Negative Syndrome Scale and Clinical Global Impression Severity scale. Other measures included functioning, subjective response and attitude toward therapy, and cognition. Laboratory tests and electrocardiography with QTc interval were carried out. Extrapyramidal symptoms and sexual dysfunction symptoms were also assessed. Of the 312 enrolled patients, 73.1% completed the study. Olanzapine, risperidone, and haloperidol were the most common psychotropic drugs taken before entry. Poor efficacy was the main reason for change in therapy. Significant improvements from baseline to endpoint were reported for mean Positive and Negative Syndrome Scale scores (P<0.0001), Clinical Global Impression Severity (P<0.0001), Global Assessment of Functioning (P<0.0001), Subjective Well-being scores (P<0.0001), and Trail Making Test (P<0.05). Significant improvements were also found for mean Simpson-Angus scale score (P<0.0001), sexual dysfunction, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. In addition, mean body weight significantly decreased from baseline (P<0.0001). A favorable profile for ziprasidone was found with regard to improved subjective tolerability, quality of life, and medication adherence behavior.